Journal of Genetics and Genomics 45 (2018) 621e638

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Journal of Genetics and Genomics

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Review Retrospective and perspective of plant in China

* * * Cheng-Guo Duan a, , Jian-Kang Zhu a, b, , Xiaofeng Cao c, a Shanghai Center for Plant Stress Biology and Center of Excellence for Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China b Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907, USA c State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academyof Sciences, Beijing 100101, China article info abstract

Article history: Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the Received 15 August 2018 DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or Received in revised form environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a 25 September 2018 octamer (two copies of H2A, H2B, H3 and H4) to form , the fundamental unit of Accepted 30 September 2018 . The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic Available online 6 November 2018 mechanisms, including DNA , histone posttranslational modifications (PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic Keywords: Plant epigenetics mechanisms participate in almost all the important biological processes ranging from basal development DNA methylation to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also Histone modifications occur in plants. Plant studies have provided numerous important contributions to the epigenetic Chromatin remodeling research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato. Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation (RdDM) pathway is plant-specific because of the in- volvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epige- netics field in China over the past several decades and give a brief outlook on future research prospects. We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms. Copyright © 2018, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.

1. General overview of plant epigenetic research in China past 40 years ranging from 1978 to 2017, including the fields of DNA methylation, histone modifications, chromatin remodeling and With the continuous improvements of sequencing technology small noncoding RNAs. We compared the total publications per and the accomplishment of the annotation of Arabidopsis genome, year in plant epigenetics with that published by Chinese re- epigenetic studies have experienced explosive growth over the past searchers or groups. We found that the majority of papers several decades. Similar situation also occurs in China, one of the contributed by China were published after the year 2000 and have major agricultural countries in the world, especially in the field of experienced a dramatical increase since then (Fig. 1A), indicating plant genetics benefiting from the growing research funding and epigenetic studies are much active during this period. Consistent the rich plant resources. Based on the public database from “Web of with this trend, total citations per year also experienced rapid in- Science”, we analyzed the publications in plant epigenetics over the crease over the past 20 years (Fig. 1B). By contrast, the increase of publications from other countries were much slower than China, although there is also a rapid increase after the year 2000 (Fig. 1A). * Corresponding authors. This trend is further supported by a sharp increase in the per- E-mail addresses: [email protected] (C.-G. Duan), [email protected] (J.-K. Zhu), centage of papers published by China over the total publications, [email protected] (X. Cao). https://doi.org/10.1016/j.jgg.2018.09.004 1673-8527/Copyright © 2018, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved. 622 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638

Fig. 1. The comparison of publications contributed by China and other countries over the past 40 years in the field of plant epigenetics. Collection of the publication information is from the public database of “Web of Science” (https://apps.webofknowledge.com/UA_GeneralSearch_input.do?product¼UA&search_mode¼GeneralSearch&SID¼6C6G thh4wqMhMnwquYs&preferencesSaved ¼ ). For the criteria of publications, only articles and conference papers are included. which arises from 0% (1978) to ~30% (2017). This data strongly epigenetic gene silencing and heterochromatin in both plants and suggests that plant epigenetic studies have been speeding up over mammals. DNA methylation is involved in multiple cellular and the past 20 years in China. About 53% papers published by China are biological processes. High level of DNA methylation is required for contributed by the top 10 research institutions (Fig. 1C). Among the silencing of transposable elements (TEs) which is important for them, Chinese Academy of Sciences (CAS), Chinese Academy of genome stability (Slotkin and Martienssen, 2007). Proper patterns Agricultural Sciences (CAAS) and China Agricultural University of DNA methylation are crucial for the precise regulation of growth (CAU) rank the first three (Fig. 1C). and development (Zilberman et al., 2007). In mammals, DNA methylation is closely linked to disease pathogenesis (e.g., cancer) 2. Dynamic regulation of DNA methylation pattern in plants and aging (Bergman and Cedar, 2013; Klutstein et al., 2016). Simi- larly, the dynamically regulated DNA methylation responds to DNA 5-methylcytosine (5mC) modification is a hallmark of environmental changes and contributes to plant stress response C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 623

(Migicovsky and Kovalchuk, 2013; Deleris et al., 2016). Disruption processed by DICER-LIKE PROTEIN 3 (DCL3) into 24-nt siRNAs, of DNA methylation often results in inheritable developmental which are then loaded onto ARGONAUTE 4 (AGO4) proteins. The defects and reprograming of gene expression. As an important siRNA-AGO4 complex is recruited by another nascent noncoding aspect of epigenetic mechanisms, DNA methylation studies in RNA transcript P5RNA, a product of Pol V which is the other plant- China have made great strides not only in the elucidation of regu- specific RNA polymerase, via sequence complementary pairing. latory mechanisms but also in the discovery of DNA methylation- Finally, AGO4 interacts with DOMAINS REARRANGED METHYLASE based novel epigenetic phenomena. With the development of 2 (DRM2) to catalyze de novo DNA methylation (Cao et al., 2003; sequencing technology, more and more crop genomes have been Law and Jacobsen, 2010; Zhong et al., 2014). Pol IV and Pol V are sequenced, the majority of which are completed by Chinese sci- each composed of twelve subunits. He et al. from Dr. Jian-Kang entists, including grain crops like wheat (Jia et al., 2013; Ling et al., Zhu's group identified NRPD4/RNA-DIRECTED DNA METHYL- 2013, 2018), vegetables like Brassica rapa (Wang et al., 2011), cu- ATION 2 (RDM2), a subunit of Pol IV, as a new component in RdDM cumber (Cucumis sativus)(Huang et al., 2009), potato (Solanum pathway using an efficient forward genetic screen (He et al., 2009a). tuberosum)(Potato Genome Sequencing et al., 2011), Carica papaya In canonical RdDM model, how Pol IV is recruited to target loci is Linnaeus (Ming et al., 2008), fruit trees like pear (Pyrus bretsch- critical for the initiation of 24-nt siRNA biogenesis and downstream neideri)(Wu et al., 2013b), and some stress resistant crops like RdDM reactions. Zhang et al. (2013b) and Law et al. (2013) inde- quinoa (Zou et al., 2017). The elucidation of these crop genomes pendently reported that the heterochromatic mark H3K9me2 could helps to investigate their epigenomes. Up to now, high resolution be bound by DNABINDING TRANSCRIPTION FACTOR 1 (DTF1)/ DNA methylomes have been sequenced in multiple plant species in SAWADEE HOMEODOMAIN HOMOLOG 1 (SHH1), which directly China. These plants include food crops like maize (Zea mays) and interacts with the chromatin remodeling protein CLASSY 1 (CLSY1) potato (S. tuberosum), vegetables like tomato (S. lycopersicum) and and Pol IV in vivo, thereby assisting the recruitment of Pol IV to cucumber (C. sativus L.), fruit trees like apple (Malus x domestica), RdDM target loci. RDM4 (He et al., 2009b)/DEFECTIVE IN MERI- and cash crops like cotton and B. napus (Zhang et al., 2014a, 2016a; STEM SILENCING 4 (DMS4) (Kanno et al., 2010), which is firstly Song et al., 2015a; Li et al., 2016a; Lai et al., 2017; Lang et al., 2017; identified by Dr. Jian-Kang Zhu's group, has been shown to interact Liu et al., 2017a, 2017c; Lu et al., 2017; Xu et al., 2017; Wang et al., with NRPE1 and NRPB1 to serve as a transcriptional regulator of Pol 2018). V and Pol II (He et al., 2009b). A study further revealed that RDM4 is also associated with NRPD1, CLSY1, RDR2 and SHH1 in vivo (Law 2.1. Establishment of DNA methylation pattern in Arabidopsis et al., 2011), suggesting that RDM4 also participates in the initia- tion of siRNA biogenesis. For the recruitment of Pol V, Liu et al. from Different from mammals in which 5mC is mainly found at CG Dr. Xin-Jian He's group and Johnson et al. from Dr. Jacobsen's group sites, DNA cytosine methylation in plants can occur in three cyto- independently reported that two SET (Su(var)3-9, E(Z) and Tri- sine contexts, CG, CHG and CHH (H represents A, T or C), which are thorax) domain proteins, SUVH2 and SUVH9, are required for the catalyzed by different DNA methyltransferases (DNMTs) (Law and occupancy of Pol V to RdDM loci (Johnson et al., 2014; Liu et al., Jacobsen, 2010). Early in 2000, Dr. Xiaofeng Cao and her col- 2014b). SUVH2 and SUVH9 lack histone methyltransferase activ- leagues described DNMT genes in model plant Arabidopsis and crop ity but are capable of binding methylated DNA and directly interact plant maize and confirmed the presence of mammalian DNMT3 with the chromatin remodeling complex DMS3-DRD1-RDM1 orthologues in plants (Cao et al., 2000). In Arabidopsis, symmetric (DDR) (Law et al., 2010) and the Microrchidia (MORC) complex, CG methylation is maintained by METHYLTRANSFERASE 1 (MET1), thereby recruiting Pol V to chromatin for DNA methylation an orthologue of the mammalian DNMT1, which recognizes hemi- (Johnson et al., 2014). In the DDR complex, DRD1 is an ATP- methylated CG double-stranded DNA and methylates unmodified dependent DNA translocase. RDM1 (also known as DMS7), which cytosine with the help of several cofactors during DNA replication is firstly identified by Dr. Jian-Kang Zhu's group, has the single- (Kankel et al., 2003; Law and Jacobsen, 2010). Symmetric CHG stranded DNA-binding activity and directly interacts with AGO4 methylation is mainly maintained by CHROMOMETHYLASE 3 and DRM2 in vivo, thereby facilitating the recruitment of DRM2 to (CMT3) which binds to repressive H3K9me2 mark and methylates the chromatin (Gao et al., 2010b; Law et al., 2010). In the MOCR unmodified CHG (Cao and Jacobsen, 2002). Methylated CHG in turn complex, MORC1, MORC2 and MORC6 have been shown to interact recruits specific histone methyltransferases, including with SUVH2/9 and are required for heterochromatin condensation SU(VAR)3-9 homolog 4 (SUVH4), SUVH5 and SUVH6, to carry out (Liu et al., 2014b; Jing et al., 2016). He et al. from Dr. Jian-Kang Zhu's H3K9 methylation. Therefore, H3K9me2 and methylated CHG group reported that KOW DOMAIN-CONTAINING TRANSCRIPTION reinforce each other to form a positive feedback loop. Dysfunctions FACTOR 1 (KTF1)/RDM3, a member of the nuclear SPT5 RNA poly- of H3K9 methyltransferases lead to genome-wide loss of CHG merase elongation factor family, recruits siRNA-AGO4 to nascent methylation (Jackson et al., 2002; Johnson et al., 2002; Ebbs et al., P5RNA by directly binding AGO4 and P5RNA transcript indepen- 2005; Ebbs and Bender, 2006). Consistently, knocking out histone dent of siRNA biogenesis to form an RdDM effector complex (He H3K9me2 demethylase IBM1 leads to dramatic increase of gene et al., 2009c). body CHG methylation (Saze et al., 2008). Argonaute (AGO) proteins play essential roles in RdDM and In plants, asymmetric de novo DNA methylation (CHH methyl- posttranscriptional gene silencing (PTGS) pathways by recruiting ation) is established through a plant-specific mechanism, 24-nt small RNAs to form the core RNA silencing complex. However, how siRNA-dependent RNA-directed DNA methylation (RdDM) different small RNAs are sorted into specific AGO complex remains pathway (Law and Jacobsen, 2010). RdDM has been the focus of largely unknown. Arabidopsis genome encodes ten AGOs which plant epigenetics over the past 15 years. Chinese researchers have play different roles in specific silencing pathways. Dr. Yijun Qi's made outstanding contributions in both the discovery of novel group revealed the importance of the 50 terminal nucleotide of the components and the deciphering of molecular mechanisms of small RNA in the sorting process in Arabidopsis (Mi et al., 2008). RdDM pathway. According to a widely accepted canonical model They revealed that AGO1 mainly harbors microRNAs which favor a (Fig. 2), Pol IV, a plant-specific multisubunit RNA polymerase, 50 terminal uridine, and AGO2 and AGO4 preferentially recruit produces noncoding transcript P4RNA at heterochromatic region small RNAs with a 50 terminal adenosine, whereas AGO5 predom- which is immediately amplified into double-stranded RNA (dsRNA) inantly binds small RNAs that initiate with cytosine (Mi et al., by RNA-DEPENDENT RNA POLYMERASE 2 (RDR2). dsRNA is 2008). The 50 end-recognition model at least partially explains 624 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638

Fig. 2. A canonical model of RNA-directed DNA methylation (RdDM) in Arabidopsis. A canonical RdDM has three major steps: Pol IV RNA transcription, de novo DNA methylation and heterochromatin formation. CG methylation maintenance with MET1 and the histone deacetylase HDA6 facilitates lysine 9 methylation (H3K9me2). DTF1/SHH1 binds the H3K9me2 mark and recruits Pol IV to the chromatin to initiate transcription. The generated short transcript P4RNA is amplified into double-stranded RNA (dsRNA) by RDR2 with the help of RDM4, or directly bound by AGO4. dsRNA is diced into 24-nt siRNAs which are loaded onto AGO4 in the cytoplasm after methylated by HEN1. The siRNA-AGO4 complex is then imported into the nucleus. SUVH2 and SUVH9 bind methylated DNA and recruit Pol V to the chromatin with the help of chromatin remodeling DDR and MORC complexes. KTF1 as a scaffold protein binds the nascent Pol V transcript P5RNA and siRNA-AGO4/6 complex to recruit DRM2 methyltransferase with the help of RDM1 for catalyzing de novo DNA methylation. The IDN2-IDP complex binds to P5RNA and interacts with SWI/SNF complex to adjust nucleosome positioning (Zhu et al., 2013). DNA methylation is amplified by SUVH4/5/6 to deposit H3K9me2 in the chromatin and form heterochromatin with the help of HDA6. The underlined RdDM components are independently identified by Chinese researchers or groups.

how different small RNA-AGO complexes mediate diverse regula- RNAs, although the detailed mechanism remains unclear (Huang tion pathways. In canonical RdDM model, AGO4 protein plays a et al., 2013). These findings suggest that RNA splicing machinery very critical role through its siRNA-binding activity and interaction is involved in promoting RdDM and transcriptional gene silencing with methyltransferase DRM2 and other factors (Zilberman et al., (TGS) (Huang and Zhu, 2014). 2003). Although RdDM is a nuclear process, evidence from Dr. Yijun Qi's group indicated that AGO4 is loaded with 24-nt siRNAs in 2.2. Removal of DNA methylation: DNA demethylation the cytoplasm and siRNA binding facilitates the translocation of AGO4 into the nucleus. Moreover, they also revealed that the for- A specific DNA methylation state is dynamically determined by mation of siRNA-AGO4 complex requires HSP90 and the cleavage DNA methylation and demethylation, two reverse biological pro- activity of AGO4 (Ye et al., 2012). AGO6, a paralogue protein of AGO4 cesses. In plants, removal of methylated cytosine can be achieved in Arabidopsis, has been considered functionally redundant with through two ways: passive demethylation which loses DNA AGO4. Contrary to this notion, AGO6 was identified from the for- methylation during DNA replication, and active demethylation ward genetic screen (Zheng et al., 2007)(Fig. 2), suggesting that which is catalyzed by a family of DNA glycosylase/lyase proteins AGO6 bears nonredundant function with AGO4 in regulating (Zhu, 2009). Arabidopsis genome encodes four DNA demethylases: RdDM. This conclusion is further confirmed by recent studies (Duan DEMETER (DME), ROS1 (DME LIKE PROTEIN 1, DML1), DML2 and et al., 2015b; McCue et al., 2015). DML3. The first evidence was reported by Dr. Jian-Kang Zhu's lab- It has been known that DCL3-dependent production of 24-nt oratory from a genetic screen for suppressor of transgene silencing siRNAs is a unique feature in the initiation of RdDM. Recent dis- (Gong et al., 2002). ROS1 dysfunction causes transgene silencing coveries from Dr. Jian-Kang Zhu's, Dr. Yijun Qi's and Dr. Jacobsen's and increases DNA methylation levels in transgene promoter and groups updated our understanding about this process. Surprisingly, thousands of endogenous loci. Compared to ROS1 which is mainly recent studies revealed that of all the Pol IV- and/or Pol V-depen- expressed in vegetable tissues, DME is preferentially expressed in dent RdDM loci, only 16% are fully dependent on the slicing of Dicer. companion cells of the female and male gametes and affects allele- Thousands of RdDM loci were identified in dcl1234 tetraploid specific expression of imprinted genes through DNA demethylation mutant, suggesting that a Dicer-independent Pol IV-RdDM mech- (Choi et al., 2002; Gehring et al., 2006). Different from DNA anism may be present (Zhai et al., 2015; Yang et al., 2016a; Ye et al., methylation which is catalyzed by single methyltransferase, the 2016). How this Dicer-independent RdDM pathway controls DNA cleavage of methylated cytosine by DNA demethylase is followed by methylation should be clarified in the future study. a sequential DNA repair reactions called base excision repair (BER) Besides the canonical components in RdDM, several RNA (Zhu, 2009). Most of the components involved in BER have been splicing-related proteins have also been identified by Chinese re- identified by Dr. Jian-Kang Zhu's group. Among them, the apurinic/ searchers to be directly/indirectly involved in the regulation of apyrimidinic endonuclease DNA-(APURINIC OR APYRIMIDINIC RdDM. Dr. Xinjian He's group revealed that STA1, a PRP6-like SITE) LYASE (APE1L) and the ZINC FINGER 30-PHOSPHATASE (ZDP) splicing factor, facilitates the production of Pol V transcripts (Dou function downstream of ROS1-mediated cleavage to remove the et al., 2013) and ZOP1, a Zinc-finger and OCRE domain-containing blocking of 30 b-unsaturated aldehyde (30-PUA) and 30 phosphate, pre-mRNA splicing factor, promotes Pol IV-dependent siRNA respectively, allowing subsequent DNA polymerization and ligation accumulation (Zhang et al., 2013a). Consistently, Dr. Jian-Kang Zhu's (Martinez-Macias et al., 2012; Li et al., 2015b). AtLIG1, one of the six group also identified a pre-mRNA-splicing factor RDM16, a DNA ligases in Arabidopsis, has been shown to be the major DNA component of U4/U6 snRNP, functioning in regulating DNA ligase functioning at the last step of BER to complete the DNA repair methylation by influencing Pol V transcript level instead of small reaction (Li et al., 2015c). All the mutants of APE1L, ZDP and AtLIG1 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 625 genes display defects in seed development due to disrupted gene involved in chromatin-mediated inheritance during DNA replica- imprinting, suggesting that these factors are also required for DME- tion. A mutation in DNA polymerase a in Arabidopsis results in the triggered DNA repair reactions in seeds. release of TGS (Liu et al., 2010b). Moreover, Dr. Zhizhong Gong's ROS1-dependent DNA demethylation displays target specificity. laboratory also found that several core DNA replication proteins TEs near protein-coding genes, especially RdDM-dependent DNA and DNA replication-related proteins, including DNA replication hypermethylation loci, are preferentially targeted by ROS1 (Tang protein A2A (RPA2A), Replication Factor C1 (RFC1) and DNA poly- et al., 2016), suggesting a potential role of ROS1 in preventing the merase ε, are directly involved in TGS and chromatin maintenance spreading of DNA methylation to protect the proper expression of (Kapoor et al., 2005; Xia et al., 2006; Yin et al., 2009; Liu et al., protein-coding genes. Qian et al. (2012) reported that a histone 2010c). Among them, RPA2A physically interacts with DNA deme- acetyltransferase INCREASED DNA METHYLATION1 (IDM1) is thylase ROS1, suggesting that DNA methylation is dynamically required for ROS1-dependent active DNA demethylation. IDM1 maintained during DNA replication (Kapoor et al., 2005; Xia et al., binds to methylated DNA at chromatin sites lacking histone H3K4 2006). di-/tri-methylation and acetylates H3 at K18 and K23 sites to create a chromatin environment for the accessibility of ROS1 to target loci. 2.3. DNA methylation-dependent posttranscriptional regulation of A substantial subset of ROS1 target loci depends on the acetyl- gene expression transferase activity of IDM1 on (Qian et al., 2012). IDM1, also known as ROS4, was also identified by Dr. Zhizhong Gong's In principal, DNA methylation often exerts deleterious effects on laboratory using a 35S-NPTII-based forward genetic screen (Li et al., gene expression at the transcriptional level due to the formation of 2012). To uncover more factors functioning upstream of ROS1 heterochromatin in hypermethylated regions. For example, ROS1 during target recognition, an efficient forward genetic screen sys- dysfunction leads to a spread of hypermethylation to the promoter tem was established in Dr. Jian-Kang Zhu's laboratory in which the region of EPF2 gene, which causes transcriptional silencing of EPF2 expression of 35S promoter-driven SUC2 transgene causes a short- (Fig. 3A) (Yamamuro et al., 2014). However, DNA methylation is root phenotype on sucrose medium. Mutations in DNA demethy- found not only in intergenic regions and gene promoters, but also in lation and anti-silencing factors will lead to increase of DNA transcribed regions, including the introns. In most cases this is methylation level in transgene promoter and silencing of SUC2 caused by the insertion of TEs or repetitive elements (To et al., transgene, and the corresponding mutants grow normally in su- 2015). Although it is not clear about the biological functions of crose medium (Wang et al., 2013b; Lei et al., 2015). Multiple anti- gene body DNA methylation, recent studies have provided impor- silencing/DNA demethylation factors have been identified from tant hints for answering this question. ANTI-SILENCING 1 (ASI1), an this screen system, including IDM2 (Qian et al., 2014), IDM3 (Lang RNA-binding protein, was firstly identified from a forward genetic et al., 2015), MET18 (Duan et al., 2015a), METHYL-CPG-BINDING screen for the factors preventing transgene silencing (Wang et al., DOMAIN 7 (MBD7) (Lang et al., 2015), HARBINGER TRANSPOSON- 2013b). Wang et al. (2013b), a Japanese group (Saze et al., 2013) DERIVED PROTEIN 1 (HDP1) and HDP2 (Duan et al., 2017a). Zhao and a France group (Coustham et al., 2014) uncovered a unique role et al. from Dr. Zhizhong Gong's group also identified IDM2 in the of ASI1, also named as INCREASE BONSAI METHYLATION 2 (IBM2) 35S-NPTII-based screen in which it was named as ROS5 (Zhao et al., and SHOOT GROWTH1 (SG1), in RNA processing and gene body 2014). Among these novel DNA demethylation regulators, IDM2, CHG methylation through an uncharacterized mechanism. In this IDM3, MBD7, HDP1 and HDP2 associate with histone acetyl- mechanism, ASI1 is required for the expression of full-length transferase IDM1 in vivo to form a protein complex and function in transcripts of the intronic heterochromatin-containing genes ROS1-dependent active DNA demethylation (Duan et al., 2017a). In through affecting the selection of proximal and distal poly- this complex, MBD7 is a methylated DNA-binding protein which adenylation sites, an RNA processing mechanism called alternative shows high binding affinity to DNA region with high methylated CG polyadenylation (APA). In asi1 mutant, truncated short transcripts density (Lang et al., 2015). HDP2 is a member of trihelix tran- are excessive accumulated whereas functional full-length tran- scription factor family with conserved MYB-like DNA-binding scripts are dramatically reduced, even completely repressed (Wang domain (Duan et al., 2017a). MBD7 and HDP2 associate with IDM1 et al., 2013b). The histone H3K9me2 demethylase gene IBM1 is a through interaction with HSP20-like chaperon proteins IDM2/3 and direct target of ASI1. Hence, asi1 mutant phenocopies ibm1 mutant scaffold protein HDP1, respectively. So, in IDM complex, DNA- in gene body CHG methylation due to the increased levels of binding proteins MBD7 and HDP2 jointly determine the target H3K9me2. Moreover, recent studies from Chinese and American specificity of IDM1-mediated histone acetylation modification, groups revealed the involvement of two new players in this thereby recruiting DNA demethylase ROS1 to specific target loci mechanism, ENHANCED DOWNY MILDEW 2 (EDM2) and ASI1- (Lang et al., 2015; Duan et al., 2017a), although the underlying IMMUNOPRECIPITATED PROTEIN1 (AIPP1) (Tsuchiya and Eulgem, recruiting mechanism is still unclear. Moreover, IDM1 only targets a 2013; Lei et al., 2014; Duan et al., 2017b). These three compo- small part of ROS1-mediated demethylation loci. Alternative nents form a protein complex in vivo, ASI1-AIPP1-EDM2 (AAE) mechanisms for ROS1 recruitment are supposed to be present and complex, in which AIPP1 serves as a bridge protein to interact with should be clarified in the future study. ASI1 and EDM2, respectively (Duan et al., 2017b)(Fig. 3B). Although Epigenetic inheritance is coupled with DNA replication. How- the detailed molecular mechanism remains unclear, current evi- ever, epigenetic marks are not always precisely copied from the dence has shown that AAE complex is specifically recruited to parental cells in each cell cycle which leads to epigenomic change- target genes through the unique chromatin structure of the intronic dependent cell differentiation or different cell responses to envi- heterochromatin in gene body. EDM2 bears three copies of plant ronmental stresses. Recently, more and more evidences have homeodomains (PHDs) and displays - and H3K9me2- revealed that DNA replication-related factors are involved in the binding affinity in vitro (Lei et al., 2015). Therefore, in this case, regulation of TGS. Evidence from Dr. Zhizhong Gong's laboratory the epigenetic marks, including DNA methylation and histone reveals that TOUSLED protein kinase, is required for the mainte- modifications, may serve as a functional module to recruit AAE nance of DNA methylation-independent TGS in Arabidopsis (Wang complex to target loci for proper RNA processing. Consistent with et al., 2007). They provided further evidence to show that DNA this notion, depletion of intronic heterochromatin represses the polymerase a, which has been shown to interact with LIKE HET- RNA processing defects caused by asi1 and edm2 mutations (Wang EROCHROMATIN PROTEIN 1 (LHP1) (Barrero et al., 2007), is et al., 2013b; Lei et al., 2014). Moreover, Rigal et al. (2012) and our 626 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638

Fig. 3. DNA methylation-dependent transcriptional gene silencing and posttranscriptional RNA processing. A: Intergenic DNA methylation spreads to promoter regions to result in transcriptional gene silencing. DNA methylation is dynamically regulated by DNA methylation and demethylation, and DNA methylation can affect DNA demethylation by regulating the transcription of DNA demethylase gene ROS1. Dysfunction of DNA demethylation will lead to the spread of DNA hypermethylation to promoter regions which represses the expression of downstream genes. Red and grey rectangles represent TEs and exons, respectively. Black arrows represent transcriptional direction. B: Posttranscriptional RNA processing mediated by intronic DNA methylation. When intronic TE is methylated, the intragenic heterochromatin will recruit ASI1-AIPP1-EDM2 (AAE) complex to this region to promote distal polyadenylation. When DNA methylation is lost in the intronic TE, failure of AAE complex recruitment will result in proximal polyadenylation. unpublished data showed that DNA methyltransferases MET1 and determined by RNA methyltransferase, 6mA-binding protein and CMT3 and histone H3K9 methyltransferases SUVH4, SUVH5 and demethylase (Fu et al., 2014). Dr. Chuan He's laboratory investi- SUVH6 are required for the accumulation of full-length IBM1 gated the genome-wide profile of 6mA methylation in Arabidopsis transcript. These evidences suggest that DNA methylation can and revealed some plant-specific features of 6mA distribution (Luo affect gene expression at both transcriptional and post- et al., 2014), revealing the conservation of RNA methylation in transcriptional levels (Fig. 3). plants. In the 6mA modifiers, Shen et al. (2016) proved that FIP37 is AAE complex-mediated heterochromatin-dependent RNA pro- a core component of 6mA methyltransferase complex and plays a cessing is involved in multiple biological processes. Besides the critical role in the regulation of shoot stem cell fate in Arabidopsis. regulation of CHG methylation through IBM1, fungal disease Dr. Guifang Jia's laboratory revealed that ALKBH10B can reverse resistance gene RPP7 is the direct target of AAE complex. edm2 6mA methylation in Arabidopsis and is required for floral transition, mutant displays similar sensitive phenotype to rpp7 mutant upon demonstrating that ALKBH10B is a 6mA RNA demethylase (Duan fungal infection (Eulgem et al., 2007). Moreover, similar phenom- et al., 2017c). Recently, Dr. Guifang Jia’ laboratory and the other enon has been reported in oil palm in which the processing of oil two groups characterized the YTH-domain family protein ECT2 as gene DEF1 is subjected to the DNA methylation levels of Karma,an the 6mA reader functioning in the regulation of trichome branching intronic LINE retrotransposon embedded in DEF1 gene body (Ong- and developmental timing in Arabidopsis (Arribas-Hernandez et al., Abdullah et al., 2015). Although AAE complex-encoding genes have 2018; Scutenaire et al., 2018; Wei et al., 2018). In addition to 6mA not been characterized in other species, our unpublished data also RNA methylation, 6mA DNA methylation has recently been shown proved the presence of orthologue protein of Arabidopsis ASI1 in oil to be an important epigenetic mark in eukaryotes. Liang et al. palm and the majority of plant species but not in mammalians, (2018) characterized the genome-wide profile of 6mA DNA suggesting that ASI1 is a plant-specific protein and ASI1-mediated methylation in Arabidopsis. They found that DNA 6mA methylation RNA processing as a novel epigenetic mechanism is conserved is enriched in gene bodies and pericentromeric heterochromatin across different plant species. regions, and is potentially associated with actively expressed genes, suggesting an important regulatory role of 6mA DNA methylation fi 3. N6-adenosine methylation in plants. Interestingly, 5mC modi cation as a well-known DNA methylation is also present in RNAs in both prokaryotes and eu- In addition to the most extensively studied DNA cytosine karyotes. Cui et al. (2017) characterized the dynamic pattern of 5mC methylation, N6-adenosine methylation (6mA), which can occur in RNA methylation in Arabidopsis. They revealed that 5mC RNA fi RNA and DNA strands, is gaining more and more attentions methylation is enriched in coding sequences and a tRNA-speci c recently. The importance of RNA methylation at N6-adenosine is methyltransferase 4B (TRM4B) shows the 5mC RNA methyl- constantly being clarified and Chinese researchers have achieved transferase activity. TRM4B is required for root development, sug- great achievements in this field. 6mA plays crucial roles in multiple gesting that 5mC RNA methylation as a new epigenetic mark plays biological processes. Pattern and function of 6mA methylation are critical roles in plant development. The researches in RNA C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 627 epigenetics field, including RNA 6mA and 5mC methylation, are still biological functions of these histone marks, it is important to un- at an early stage, and largely is unknown about the underlying cover and characterize the factors involved in the establishment, molecular mechanism, such as the establishment, recognition and recognition and removal of these epigenetic information. Table 1 remove of this RNA epigenetic mark. The identification of new summarizes the known histone lysine methylation modifiers in components involved in the dynamic process and the discovery of Arabidopsis and rice. its biological functions would be an important focus in the future Writers: Most of the histone lysine methylation is catalyzed by a epigenetic research. family of SET domain-containing proteins in Arabidopsis and rice (Zhao and Shen, 2004; Liu et al., 2010a). There are 49 SET domain- 4. Histone modifications containing proteins in Arabidopsis, known as the SET DOMAIN GROUP (SDG) proteins, which can be classified into five groups Histone modifications refer to the posttranslational covalent based on their activity and domain architecture (Zhao and Shen, modifications on the amino-terminal tails of the core histones. 2004). Among them, H3K9 methylation is achieved by SUVH pro- Histone posttranslational modifications (PTMs) serve as histone teins. KRYPTONITE (KYP; also known as SUVH4) functions partially code to constitute the other layer of epigenetic mechanism. These redundant with SUVH5 and SUVH6 to catalyze H3K9 methylation. PTMs include acetylation, methylation, ubiquitination, sumoyla- Genome-wide loss of DNA methylation at all cytosine contexts tion, and phosphorylation. Regulation of histone modifications has were observed in the suvh4/5/6 triple mutant. In 2001, Shen iden- been extensively investigated. Among different histone modifica- tified the SET domain-containing proteins in tobacco and Arabi- tions, , which not only occurs at different res- dopsis which show highest homologies with the Drosophila idues (lysine and arginine) and different sites but also differs in the SU(VAR)3-9 protein (Shen, 2001). Liu et al. from Dr. Wen-Hui number of added methyl groups, plays an essential role in multiple Shen's laboratory and Ding et al. from Dr. Xiaofeng Cao's labora- biological processes, including transcriptional regulation of TEs and tory identified NtSET1 in tobacco and SDG714 in rice as H3K9 protein-coding genes during plant development and stress methyltransferases functioning in heterochromatin formation response (Liu et al., 2010a). Among different histone , (Ding et al., 2007; Liu et al., 2007b). histone lysine methylation is widely investigated due to its As another repressive histone mark, H3K27 can be mono-, di- or important roles in both transcriptional activation and repression. In tri-methylated in Arabidopsis. Similar to H3K9me1/2, H3K27me1 is plants, histone H3 lysine methylation occurs at four sites, 4, 9, 27 enriched at constitutively silenced heterochromatin regions, and 36. The function of histone methylation is dependent of the whereas is enriched in euchromatin regions in plants sites of methylated lysine residues and the number of methyl (Fuchs et al., 2006). In Arabidopsis, H3K27me1 is catalyzed by groups. For example, H3K9 and H3K27 methylations are generally ARABIDOPSIS TRITHORAX-RELATED PROTEIN5 (ATXR5) and ATXR6 considered as repressive marks which are often associated with (Jacob et al., 2009). Different from H3K9me2 which affects DNA silenced regions, while H3K4 and H3K36 methylations are enriched methylation, H3K27me1 is DNA methylation-independent and its in actively expressed genes. H3K9me2 is enriched in chromocen- deposition is not affected by the depletion of H3K9me2. Zhang et al. ters, where TEs and repeated sequences are enriched and DNA (2007a) investigated the genome-wide distribution of H3K27me3 maintains hypermethylated. Loss of H3K9me1/2 results in reduced and found that H3K27me3 is preferentially enriched in the tran- non-CG DNA methylation and released silencing of TEs. In these scribed region of coding genes, indicating a major repressive role on loci, H3K9 methylation interplays with DNA methylation to rein- gene expression in Arabidopsis. H3K27me3-dependent gene force each other. Similar to DNA methylation, histone methylation silencing is achieved mainly through two polycomb group (PcG) pattern is dynamically regulated by histone methylase (writer) and repressive complexes (PRCs), PRC2 and PRC1. PRC2 is a H3K27me3 demethylase (eraser)-mediated enzymatic reactions. Different methylation complex in which CLF, MEA and SWN are believed to histone methylation modifications can be bound by reader protein be H3K27me3 methyltransferases in Arabidopsis (Luo et al., 1999; to recruit downstream factors. To better understanding the Wang et al., 2006; Kim and Sung, 2014). The deposition of

Table 1 Characterized modifiers of histone lysine methylation (HKM) in Arabidopsis and rice.

HKM Species Writer Reader Eraser

H3K4 Arabidopsis ATX1 (Pien et al., 2008) SDG8 (Hoppmann et al., 2011) LDL1 (Spedaletti et al., 2008) ATX2/SDG30 (Saleh et al., 2008) ALs (Lee et al., 2009) JMJ14 (Lu et al., 2010) ATX3/4/5 (Chen et al., 2017) AtING (Lee et al., 2009) JMJ18 (Yang et al., 2012a) SDG4/ASHR3 (Cartagena et al., 2008) WDR5a (Jiang et al., 2009) JMJ15/MEE27 (Liu et al., 2010a; Yang et al., ATXR3/SDG2 (Guo et al., 2010) SHL (Lopez-Gonzalez et al., 2014; Qian et al., 2018) 2012b) ATXR7/SDG25 (Tamada et al., 2009) EBS (Lopez-Gonzalez et al., 2014) Rice SDG701 (Liu et al., 2017b) SDG725 (Liu and Huang, 2018) JMJ703 (Cui et al., 2013) CHR729/CHD3 (Hu et al., 2012) H3K9 Arabidopsis KYP/SUVH4 (Jackson et al., 2002) EDM2 (Tsuchiya and Eulgem, 2013; Lei et al., 2014) IBM1/JMJ25 (Saze et al., 2008) SUVH5 (Ebbs and Bender, 2006) CMT2/3 (Du et al., 2012; Stroud et al., 2014) JMJ27 (Dutta et al., 2017) SUVH6 (Ebbs et al., 2005) SHH1/DTF1 (Law et al., 2013; Zhang et al., 2013b) SUVR4 (Thorstensen et al., 2006) Rice SDG714 (Ding et al., 2007) JMJ706 (Sun and Zhou, 2008) H3K27 Arabidopsis ATXR5, ATXR6 (Jacob et al., 2009) LHP1 (Turck et al., 2007; Zhang et al., 2007b; Exner JMJ12/REF6 (Lu et al., 2011) CLF/SDG1 (Schonrock et al., 2006; Schubert et al., 2009) et al., 2006) SHL (Qian et al., 2018) MEA (Grossniklaus et al., 1998) CYP71 (Li et al., 2007) SWN (Chanvivattana et al., 2004) Rice CHR729/CHD3 (Hu et al., 2012) JMJ705 (Li et al., 2013) H3K36 Arabidopsis SDG8/ASHH2 (Xu et al., 2008) MRG1/2 (Bu et al., 2014) SDG4/ASHR3 (Cartagena et al., 2008) Rice SDG725 (Sui et al., 2012)

Bold literatures represent publications contributed by Chinese researchers or groups. 628 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 repressive H3K27me3 recruits PRC1 complex to the target chro- interaction with H3K27me3 (Liu and Min, 2016). Biochemical and matin to catalyze mono-ubiquitination of H2A (H2Aub1) (Kim and structural evidence has revealed that both the chromodomains and Sung, 2014). Liang et al. (2003) and Luo et al. (2009) characterized bromo-adjacent homology (BAH) domains of CMT2/3 DNA meth- the homologs of PcG genes in rice and revealed important regula- yltransferases bind to H3K9me2 (Du et al., 2012; Stroud et al., 2014). tory roles of H3K27me3 in multiple developmental processes in PHD domain is a zinc-binding domain and one major function of rice. PHD domain is histone binding. A lot of PHD domain-containing Compared to repressive H3K9 and H3K27 methylation marks, histone readers have been identified in Arabidopsis, such as the H3K4 methylation is widely believed to be involved in transcription H3K4me2/3 readers INHIBITOR OF GROWTH 1/2 (ING1/2) and activation. /2/3 are highly enriched in genic regions but Alfin1-like (AL) family proteins (Liu and Min, 2016). The biochem- depleted in TEs, among which H3K4me3 is present exclusively on ical and ChIP data from Dr. Jian-Kang Zhu's laboratory and the other active genes and H3K4me1/2 occur on both active and inactive group revealed that the chromatin regulator EDM2, which bears genes (Liu et al., 2010a). Methylation of H3K4 is catalyzed by the three copies of PHD domains, binds to H3K9me2 and functions in highly evolutionarily conserved COMPASS or COMPASS-like H3K4 APA regulation (Lei et al., 2014; Tsuchiya and Eulgem, 2013). methyltransferase complexes, in which a Trithorax group (TrxG) CHD (chromodomain, helicase/ATPase and DNA binding H3K4 methyltransferase and a core structural subcomplex are domain) and MRG (morf-related gene) proteins also belong to the included (He, 2012). In Arabidopsis, there are five ARABIDOPSIS chromodomain proteins. It has been reported that some reader TRITHORAX proteins (named ATX1‒5) and seven ATX-related proteins are capable of recognizing two or more histone marks proteins (named ATXR1‒7). ATX1/SDG27, ATX2/SDG30 and (Wang and Patel, 2011). Dr. Ai-Wu Dong's laboratory revealed that ATXR7/SDG25 have been shown to display H3K4 methyltransferase the MRG group proteins MRG1 and MRG2 act as the readers of activity (Chen et al., 2017). Dr. Xiaoyu Zhang's laboratory identified H3K4me3/H3K36me3 dual marks and function in photoperiod- ATXR3/SDG2 as a specific H3K4me3 methyltransferase (Guo et al., dependent flowering time regulation (Bu et al., 2014). In rice, 2010). Dysfunction of ATXR3 leads to a dramatic reduction of CHR729/CHD3 interacts with H3K4me2 and H3K27me3 through its H3K4me3 in vivo and severe developmental defects. Recently, Chen chromodomain and PHD domains, respectively (Hu et al., 2012), et al. from Dr. Yan He's laboratory revealed that ATX3, ATX4 and suggesting that CHR729 is a bifunctional chromatin regulator ATX5 function redundantly to methylate H3K4 (Chen et al., 2017). capable of recognizing and modulating H3K4 and H3K27 methyl- Song et al. from Dr. Jian-Xiang Liu's laboratory identified that basic ation dual marks. More recently, Qian et al. (2018) identified a leucine zipper (bZIP) transcription factors bZIP28 and bZIP60 plant-specific histone modification reader SHORT LIFE (SHL) in interact with COMPASS-like components to regulate the deposition Arabidopsis which recognizes dual marks, H3K4me3 and of H3K4me3 at specific gene promoters (Song et al., 2015b). In rice, H3K27me3. SHL bears BAH and PHD domains, and the PHD domain SDG701 has been characterized to catalyze H3K4 methylation and has been shown to bind to H3K4me2/3 in vitro (Lopez-Gonzalez functions in regulation of flowering and development (Liu et al., et al., 2014). Qian et al. (2018) provided structural and biochem- 2017b). ical evidence that the BAH domain of SHL is capable of binding to For H3K36 methylation, Dr. Wen-Hui Shen's laboratory provided H3K27me3. They further proved that SHL-bound genes colocalize experimental evidence that SDG8 is a major methyltransferase with H3K4me3 and H3K27me3, suggesting that SHL modulates specific for di- and tri-methylation of H3K36 (Xu et al., 2008). Li gene expression through the recognition of antagonistic histone et al. from Dr. Yuehui He's laboratory revealed that the evolution- marks. EARLY BOLTING IN SHORT DAYS (EBS), the paralogue of SHL arily conserved nuclear mRNA cap-binding complex (CBC) interacts in Arabidopsis, also bears both BAH and PHD domains. In vitro pull- with COMPASS-like complex and a histone H3K36 methyl- down assay has proved that the PHD domain of EBS binds to transferase to form a multi-protein complex and functions in the H3K4me2/3, although the binding specificity of its BAH domain has co-transcriptional mRNA processing and cap preservation. In this not been determined (Lopez-Gonzalez et al., 2014). These findings mechanism, histone methyltransferases are required for CBC- suggest that dual recognition of different histone marks may be a mediated mRNA cap preservation and proper RNA splicing, there- general epigenetic mechanism in the fine-tuning regulation of their fore revealing a novel role for active histone marks in RNA pro- associated genes. cessing (Li et al., 2016b). In rice, Sui et al. (2012) reported SDG725 as The Tudor domain is a reader of lysine or arginine methylation a H3K36 methyltransferase. marks. Arabidopsis genome encodes 32 Tudor domain-containing Readers: The epigenetic information of different histone marks proteins, and most of them have not been characterized. Recently, can be translated by reader proteins to direct downstream func- a SAWADEE domain protein SHH1 has been shown as a H3K9 tions. To a certain extent, it is the readers/effectors which ulti- methylation reader functioning in RdDM through its interaction mately determine the biological outcome of certain histone PTMs. with Pol IV (Law et al., 2011; Zhang et al., 2013b). Structural studies Different reader proteins exhibit distinct binding specificity to have revealed that the SAWADEE domain of SHH1 adopts a tandem histone marks. According to current knowledge, the known readers Tudor-like fold with a unique zinc finger embedded in the second can be classified into three groups. The first group is the royal Tudor-like domain (Law et al., 2013; Zhang et al., 2013b). family domain group proteins which share a conserved structural Arabidopsis genome encodes two WDR5 homologues, WDR5a core and have been shown to be readers of methylated histones, and WDR5b. However, only WDR5a has been shown to bind to including chromodomain, Tudor domain (also known as Agenet H3K4me2 mark and interact with H3K4 methyltransferase ATX1 domain in plants), MBT (malignant brain tumour) domain and (Jiang et al., 2009). WDR5a is required for the recruitment of PWWP (Pro-Trp-Trp-Pro) domain (Liu et al., 2010a; Liu and Min, COMPASS-like complex and promotes the expression of flowering 2016). The second group is the plant homeodomain (PHD) finger repressor FLOWERING LOCUS C (FLC). Dr. Sheng Luan's laboratory group proteins. WD40 repeat-containing WDR5 group belongs to revealed that a WD40 protein CYP71 interacts with H3K27me3 the third group (Liu et al., 2010a). In the first group of chromodo- through its WD40 domain (Li et al., 2007). main proteins, the chromodomain-containing protein LHP1 as a The CW (Cys-Trp) domain is a zinc-binding domain which is component of PRC1-like complex in Arabidopsis shows binding composed of approximately 50e60 residues. Recently, CW protein specificity to H3K27me3 in vivo (Turck et al., 2007; Zhang et al., has been shown to be a H3K4 methylation reader (He et al., 2010; 2007b). Interestingly, HP1, the mammalian counterpart of Arabi- Hoppmann et al., 2011; Liu et al., 2016b). The CW domain displays dopsis LHP1, is a H3K9me2/3 reader and shows much weaker different preference for the degree of H3K4 methylation. C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 629

Arabidopsis genome encodes 11 CW domain-containing proteins. long-day photoperiod and GA pathway (He, 2015). In FRI-mediated The histone H3K36 writer SDG8/ASHH2 has been proved to bind to activation of FLC, multiple active histone modifications are H3K4me1 mark (Hoppmann et al., 2011; Liu and Huang, 2018). recruited to FLC locus, including H3K4me3, H3K36me3 and histone Consistently, Liu and Huang (2018) reported that SDG725, the ho- acetylation marks. H3K4me3 is mainly enriched in the region molog of SDG8 in rice, displays similar preference for H3K4me1. around the transcription start site (TSS) of FLC. The deposition of Erasers: Histone demethylation is catalyzed by two types of H3K4m3 on FLC chromatin requires a COMPASS-like H3K4 meth- erasers (demethylases) with different mechanisms, amine oxida- yltransferase complex. Dr. Yuehui He's laboratory revealed that tion by lysine-specific demethylase 1 (LSD1) family proteins and COMPASS-like complex in Arabidopsis contains at least four sub- hydroxylation by JumonjiC (JmjC) domain-containing proteins units, a SET domain-containing H3K4 methyltransferase and three (JMJs) (Liu et al., 2010a). LSD1 family demethylases act on di- and structural components including WDR5a, RBBP5 LIKE (RBL) and mono-methylation, whereas JMJ demethylases act on all three ARABIDOPSIS ASH2 RELATIVE (ASH2R) (Jiang et al., 2009, 2011). kinds of lysine methylation (Klose and Zhang, 2007). Four homo- H3K4me3 writer ATX1 has been shown to be associated with logs of LSD1 are encoded by Arabidopsis genome, including WDR5a in the COMPASS-like complex (Jiang et al., 2009). Besides FLOWERING LOCUS D (FLD), LSD1-LIKE1 (LDL1), LDL2 and LDL3. COMPASS-like complex-dependent H3K4me3, the activation of FLC Among them, LDL1 and FLD have been shown to bear H3K4 expression in plants encoding FRI also requires the depositions of demethylase activity (Jiang et al., 2007; Liu et al., 2007a). Arabi- H3K36me3 and histone variant H2A.Z (Choi et al., 2007; Xu et al., dopsis and rice genomes 21 and 20 JMJs, respectively (Lu 2008). H3K36me2/3 are catalyzed by SDG8/EFS, a homolog of the et al., 2008a). These JMJs can be classified into five groups ac- yeast SET2 histone methyltransferase, in FLC locus (Xu et al., 2008). cording to sequence similarities, KDM3, KDM4, KDM5, KDM6 and Zhao et al. (2005) reported that loss-of-function mutant of SDG8 JmjC domain-only groups. Among them, several members have displays attenuated expression of FLC due to reduced H3K36me2 been identified as histone demethylases by Chinese researchers. Lu accumulation. et al. from Dr. Xiaofeng Cao's laboratory proved that JMJ14, one of For the flowering of winter annual plants, vernalization is the six homologs of KDM5 group, is an active histone H3K4 required to silence FLC expression, which is achieved by long demethylase involved in flowering time regulation through the noncoding RNAs (lncRNAs) and PRC complex-mediated deposition repression of floral integrators (Lu et al., 2010). Recently, the crystal of H3K27me3 mark at FLC locus. The silencing of FLC is stably structure of JMJ14 catalytic domain revealed by two Chinese groups maintained during the subsequent growth and development upon indicated that the critical acidic residues are conserved in plants return to warm temperature. It is still not fully understood about and animals, suggesting a common substrate recognition mecha- how PcG complex is recruited to FLC locus and the spreading of nism for KDM5 group histone demethylases (Yang et al., 2018). repression. Polycomb response elements (PREs) have been shown JMJ18, another KDM5 group protein, has been identified as a his- to function in PcG complex recruitment in Drosophila melanogaster tone H3K4 demethylase in Arabidopsis. JMJ18 is predominantly by directly interacting with PcG factors, which have not been found expressed in phloem companion cells and promotes the floral in other species. Recently, Dr. Yuehhui He's laboratory identified a transition by directly binding FLC chromatin for H3K4 demethyla- 47-bp FLC silencing element which could be recognized by tion (Yang et al., 2012a). JMJ11/ELF6 and JMJ12/REF6 are two sequence-specific readers VIVIPAROUS1/ABI3-LIKE1 (VAL1) and members of KDM4 group. Dysfunctions of JMJ11 and JMJ12 display VAL2. VAL1 and VAL2 bind this cis-element and H3K27me2/3 early and late flowering phenotypes, respectively (Yu et al., 2008). marks and recruit PcG complex to the nucleation region of FLC locus Dr. Xiaofeng Cao's laboratory revealed that JMJ12/REF6 is a histone by directly interacting with LHP1 (Yuan et al., 2016). In the dynamic H3K27me2/3 demethylase (Lu et al., 2011), which is the first his- regulation of FLC during lifecycle, another remaining question is tone H3K27 demethylase identified in plants and fills a major gap of how FLC silencing is reset during each generation. Evidence from the dynamic regulation of H3K27me3. In rice, Dr. Xiaofeng Cao's the same group revealed that a seed-specific transcription factor laboratory reported that OsJMJ703 is an active H3K4-specific LEAFY COTYLEDON1 (LEC1) could reverse the silencing of FLC demethylase which is required for TE silencing, suggesting a role inherited from gametes by promoting the initial establishment of of histone demethylase in the right control of TE (Cui et al., 2013). an active chromatin state at FLC, leading to transmission of the Dr. Dao-Xiu Zhou's laboratory revealed that the rice JMJ706, one of embryonic memory of FLC activation to post-embryonic stages (Tao the JMJD2 family proteins, specifically reverses di- and tri- et al., 2017). This finding reveals a mechanism for the reprogram- methylation of H3K9 (Sun and Zhou, 2008). Loss-of-function mu- ming of embryonic chromatin states in plants and provides insights tations of JMJ706 gene result in severe development defects, sug- into the epigenetic memory of embryonic active gene expression in gesting that histone demethylases are involved in the post-embryonic phases. developmental regulation in rice. Li et al. from the same laboratory Through the photoperiod pathway, inductive day lengths also revealed that JMJ705 catalyzes the removal of tri-methylation promote flowering by triggering the production of florigen. In of H3K27 and functions in defense-related gene activation in rice (Li long-day plant Arabidopsis, the expression of major florigen FT is et al., 2013). rhythmically activated by CONSTANS (CO), the output of the photoperiod pathway, specifically at the end of long days. Gu et al. 5. Epigenetic mechanisms in flowering time regulation (2013) reported a periodic histone deacetylation mechanism for the photoperiodic regulation of FT expression. They found that a The floral transition is a major developmental switch in angio- histone deacetylase (HDAC) complex, which includes SAP30 sperms. This biological process is tightly controlled by multiple FUNCTION-RELATED 1 (AFR1) and AFR2, is recruited by the MADS- mechanisms, including environmental (temperature, photoperiod domain transcription factor AGAMOUS LIKE 18 (AGL18) to FT and vernalization) and genetic (autonomous pathway, gibberellin chromatin specifically at the end of long days, resulting in histone (GA) pathway and FRIGIDA (FRI) pathway) factors. In Arabidopsis, deacetylation and attenuated expression of FT (Gu et al., 2013). the flowering repressor FLC is a convergent point of several flow- Moreover, during this regulation, the activity of CO is required for ering pathways. The expression of FLC is promoted by FRI and the recruitment of this HDAC complex (Gu et al., 2013), suggesting repressed by autonomous pathway and vernalization (He, 2012). that CO bears two different mechanisms to achieve a precise The expression of FLOWERING LOCUS T (FT), which encodes the regulation of flowering time in response to the inductive long-day major component of florigen, is repressed by FLC but promoted by condition. Moreover, Dr. Ai-Wu Dong's laboratory revealed that 630 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 the H3K4me3/H3K36me3 readers MRG1 and MRG2 physically photoperiod. This finding suggests that PRC2-dependent interact with CO to activate FT expression, thereby promoting silencing of gene expression plays important roles in the accu- flowering in long-day photoperiod (Bu et al., 2014). In the regu- rate photoperiod control of rice flowering. lation of photoperiod-dependent CO, recent studies revealed that nuclear factor Y (NF-Y), a heterotrimeric transcription factor 6. Epigenetic regulation in plant development complex which binds to the CCAAT motif, is also involved. Hou et al. (2014) reported that NF-Y in Arabidopsis interacts with CO 6.1. DNA methylation and plant development in the photoperiod pathway and DELLAs in the GA pathway to regulate the transcription of floral pathway integrator SUPPRES- Although there is no clear evidence of resetting of DNA SOR OF OVEREXPRESSION OF CO1 (SOC1) by directing binding to a methylation during plant development, recent studies revealed a unique cis-element within its promoter. They further revealed tight control of DNA methylation levels in different tissues and cell that NF-Y protein NF-YC counteracts the deposition of H3K27me3 types during plant development. Gene imprinting, a mechanism of in FT by temporal interaction with CLF, thereby attenuating the parental allele-specific expression which plays key roles in seed association of CLF with FT chromatin under long-day condition development, is closely associated with DME-dependent DNA (Liu et al., 2018a). demethylation and siRNA-dependent RdDM pathway (Gehring Besides histone methylation of H3K4, H3K36 and H3K27, several et al., 2004, 2006; Kinoshita et al., 2004). Dr. Jinsheng Lai's group other histone modifications also participate in the regulation of revealed that gene imprinting in maize is tightly controlled through floral transition in Arabidopsis. For example, Luo et al. (2015) re- complex interactions between multiple epigenetic mechanisms, ported that histone deacetylase HDA5 interacts with FVE, FLD, and including small RNAs, nucleosome positioning, DNA and histone HDA6 and binds to FLC, therefore negatively regulating its expres- methylation (Zhang et al., 2011, 2014a; Dong et al., 2017, 2018). sion. Therefore, hda5 mutant displays a late flowering phenotype. Besides gene imprinting in seed, lots of efforts have been made to Su et al. (2017) reported that a plant-specific histone H2A phos- investigate the tissue-specific DNA methylation patterns in plants, phorylation on serine 95 (H2AS95) catalyzed by MUT9P-LIKE- including major crops maize, rice and soybean (Xiong et al., 1999; Li KINASE (MLK4) is involved in photoperiod-dependent regulation et al., 2008; Lu et al., 2008b; Xu et al., 2009; Gao et al., 2010a; He of flowering time in Arabidopsis. mlk4 mutant displays late flow- et al., 2011). In rice, Zhang et al. (2015) revealed a role of DNA ering phenotype under long-day but not short-day conditions. They methylation in the regulation of rice RELATED TO ABI3/VP1 6 (RAV6) revealed that MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 gene which encodes a B3 DNA-binding protein and controls mul- (CCA1) which interacts with SWI2/SNF2-RELATED 1 (SWR1) com- tiple agronomical traits. These studies demonstrate a close rela- plex. This interaction allows MLK4 to bind to the GIGANTEA (GI) tionship between DNA methylation levels and tissue-specific gene promoter, thereby promoting the deposition of H2A.Z and histone expression. acetyltransferase activity and resulting in reduced expression of GI Benefiting from the elucidation of more and more crop genomes (Su et al., 2017). and the development of CRISPR/Cas9-mediated gene editing tech- In rice (Oryza sativa), similar epigenetic mechanisms are pre- nology, generation of loss-of-function mutants in crop plants be- sent in the regulation of heading date. There is also a COMPASS- comes possible. Although most of the DNA methylation-related like complex required for promoting flowering (Jiang et al., mutants in Arabidopsis grow normal or display mild developmental 2018a). In this complex, OsTrx1/SDG723 interacts with OsW- defects, disruption of DNA methylation often results in severe DR5a and a transcription factor SDG723/OsTrx1/OsSET33 INTER- developmental abnormalities in crops, and some are even lethal, ACTION PROTEIN 1 (SIP1), allowing OsTrx1 to bind to Early suggesting more important roles of DNA methylation in crop heading date 1 (Ehd1) which encodes a positive regulator of FT- development. In tomato, Zhong et al. (2013) characterized the DNA like protein in rice (Jiang et al., 2018a, 2018b). Liu et al. (2017b) methylome of fruit and found a strong correlation between DNA revealed that the H3K4 methyltransferase SDG701 in rice pro- methylation level and fruit development. Consistent with this motes photoperiod-independent flowering through enhancing notion, Lang et al. (2017) reported that tomato SlDML2, one of the the expression of Heading date 3a (Hd3a) and RICE FLOWERING orthologous proteins of Arabidopsis DNA demethylase ROS1, is LOCUS T1 (RFT1) florigens. Similarly, Liu et al. (2016a) identified required for the fine-tuned expression of ripening-induced and SDG708 as an H3K36 methyltransferase in rice. Knocking down -repressed genes. Expression of SlDML2 is dramatically increased in SDG708 causes photoperiod-independent late flowering in rice ripening tomato fruits, which promotes active DNA demethylation due to the down-regulation of H3K36me3 levels on several key and modulates the expression of ripening-induced or -repressed flowering genes, including Hd3a, RFT1 and Ehd1. Different from genes. Besides fruit ripening, Zhang et al. (2016a) reported that Arabidopsis, evidence from Dr. Hong-Wei Xue's laboratory chilling-induced tomato flavor loss is associated with reduced revealed that PRC2 is involved in photoperiod-dependent flow- accumulation of key volatile synthesis enzyme-coding genes ering regulation (Wang et al., 2013a). They found that the accompanied with dramatical changes of DNA methylation status expression of VERNALIZATION INSENSITIVE 3-LIKE 3 (OsVIL3) and in the promoters of these genes. The involvements of DNA OsVIL2, the putative components of PRC2 complex in rice, is methylation-dependent regulation in fruit are also observed in induced by short-day photoperiod. LC2 and OsVIL2 promote other fruits. Strong correlations were observed between DNA flowering by depositing H3K27me3 mark on floral repressor gene methylation pattern and the fruit size of apple and tomato (Telias OsLF which encodes a repressor of Hd1. Evidence from Dr. Dao-Xiu et al., 2011; Liu et al., 2012a; Daccord et al., 2017). These evi- Zhou's laboratory further revealed that SDG711 and SDG718, the dences suggest that specific DNA methylation patterns are required other two PRC2 components in rice, are required for photoperiod- for the development of fruits. dependent regulation of key flowering genes (Liu et al., 2014a). The expression of SDG711 and SDG718 is induced by long-day and 6.2. Histone modifications, chromatin remodeling and plant short-day photoperiods, respectively. SDG711 and SDG718 repress development the expression of floral repressor gene OsLF through mediating H3K27me3 deposition in long-day and short-day photoperiods, Epigenetic mechanisms not only participate in the regulation respectively, leading to higher expression of Hd1 thus late flow- of heading date in rice but also is required for floral development. ering in long-day photoperiod and early flowering in short-day The floral meristem (FM), which develops from inflorescence C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 631 meristem (IM) upon completion of the floral transition, termi- complex protein EMF1 and the TrxG factors ATX1 and ULTRA- nates after producing a defined number of floral organs. WUSCHEL PETALA1 (ULT1) are able to bind the chromatin of seed genes, (WUS) encodes a homeodomain-containing protein and plays a and ULT1 physically interacts with EMF1 and ATX1, suggesting critical role in the establishment and maintenance of shoot apical that they function together to modulate the expression of seed meristem (SAM), IM, and FM as well as FM determinacy. The genes (Xu et al., 2018). In the process of plant germ-line speci- expression of WUS is dynamically regulated by multiple epige- fication, Zhao et al. (2018) reported that histone variant H2A.Z netic mechanisms, including DNA methylation, H3K9 and H3K4 deposition mediated by SWR1 chromatin remodeling complex is methylation as well as histone acetylation (Li et al., 2011). The required for the expression of WRKY28 which functions through WUS-related homeobox 11 (WOX11) directly interacts with repressing hypodermal somatic cells from acquiring megaspore H3K27me3 demethylase JMJ705 to activate gene expression dur- mother cell-like cell identify. ing shoot development in rice (Cheng et al., 2018). Moreover, in In PRC complex-mediated gene suppression, although it is Arabidopsis, MET1-mediated DNA methylation is involved in the known that PRC1-mediated H2Aub1 is a key epigenetic mark in regulation of AUXIN RESPONSE FACTOR3 (ARF3) expression, Polycomb silencing, how H2Aub1 is read to direct downstream suggesting a role of DNA methylation in auxin signaling- functions remains unclear. The human ZUOTIN-RELATED FACTOR 1 dependent de novo shoot regeneration (Li et al., 2011). In rice, (ZRF1) has been shown to bind H2Aub1 via UBIQUITIN-BINDING Dr. Jianmin Wan's group identified DEFORMED FLORAL ORGAN1 DOMAIN (UBD) and favor H2Aub1 deubiquitination, leading to (DFO1) gene which functions in the regulation of floral organ the switch from repressive to active chromatin state. Dr. Wen-Hui identity (Zheng et al., 2015). They revealed that DFO1 interacts Shen's laboratory revealed that AtZRF1a and AtZRF1b, the Arabi- with the rice PcG proteins MULTICOPY SUPPRESSOR OF IRA1 dopsis homologs of animal ZRF1, participate in multiple develop- (OsMSI1) and ENHANCER OF ZESTE (E(Z)) 1 (OsiEZ1) to mediate mental processes, including seed germination, plant growth, floral H3K27me3 deposition in the chromatin of OsMADS58, one of the development and embryogenesis (Feng et al., 2016). They further MADS-box genes which control floral organ specification. Evi- proved that the developmental regulation is achieved by AtZRF1a/ dence from Dr. Zuhua He's laboratory revealed that CURVED b-mediated H2Aub1 and H3K27me3 deposition in gene suppres- CHIMERIC PALEA 1 (CCP1), the Arabidopsis EMBRYONIC FLOWER1 sion, suggesting that AtZRF1a/b may serve as a reader of H2Aub1 in (EMF1)-like protein in rice, functions in palea development developmental regulation. through mediating the deposition of H3K27me3 on the chromatin Besides DNA methylation, histone modifications and chromatin of OsMADS58 (Yan et al., 2015). Liu et al. (2015) reported that remodeling, recent studies revealed that some lncRNAs also play SDG711-mediated H3K27me3 deposition and JMJ703-mediated important roles in plant development. Systematic analysis of demethylation of H3K4me3 have agonistic functions in the lncRNAs in Arabidopsis and rice has been conducted in Dr. Xing- regulation of rice IM development. Different from Arabidopsis in Wang Deng's laboratory (Liu et al., 2013; Wang et al., 2014c). One which H3K27me3 and DNA methylation are generally mutually of regulatory mechanisms of lncRNAs is to serve as target mimicry exclusive, Zhou et al. (2016) reported that SDG711-mediated of endogenous miRNAs (Wu et al., 2013a). Zhang et al. (2014b) re- H3K27me3 mark cooperates with DRM2-mediated non-CG DNA ported that some rice lncRNAs serve as competing RNAs to methylation to regulate the expression of developmental genes sequester endogenous miRNAs. One lncRNA, XLOC_057324, has through direct interaction between SDG711 and DRM2 in rice been shown to be involved in panicle development (Zhang et al., (Zhou et al., 2016). Knockout of OsDRM2 disrupts the binding of 2014b). Wang et al. from Dr. Xing-Wang Deng's group revealed SDG711 to target genes and leads to loss of H3K27me3, suggesting that an Arabidopsis lncRNA, HIDDEN TREASURE 1 (HID1), promotes a different functioning mode of H3K27me3 in rice. In anther photomorphogenesis in continuous red light by interacting with development, Cao et al. (2015) reported that H2B mono- the transcription factor PIF3 (Wang et al., 2014b). These results ubiquitination (H2Bub1) is involved in late anther development in suggest that lncRNAs are an important aspect of plant rice. O. sativa HISTONE MONOUBIQUITINATION1 (OsHUB1) and development. OsHUB2-mediated H2Bub1 acts together with H3K4me2 in the chromatins of tapetum degradation-related genes, thereby 7. Epigenetic regulation of plant stress responses modulating the transcriptional regulation of anther development in rice. 7.1. Epigenetic regulation in abiotic stress responses Before the reproductive phase, plants first transit from a juvenile vegetative phase of development to an adult vegetative phase of Epigenetic regulation of plant responses to environmental development, and miR156 plays crucial roles in this process. A stresses has been a fascinated research partially due to the concept recent study demonstrated that the expression of miR156 is regu- of stress memory. In some cases, the transcriptional regulation of lated by a SWI2/SNF2 chromatin remodeling ATPase BRAHMA stress response genes is associated with DNA methylation with (BRM) (Li et al., 2015a), suggesting an important involvement of general or locus-specific manner. Recent studies revealed impor- ATPase-based chromatin remodeling in floral transition. tant involvements of DNA methylation in high temperature (HT) In phytohormone-mediated plant growth and development, Sui stress in cotton (Gossypium hirsutum) and Brassica plants (Li et al., et al. (2012) reported that the H3K36 methyltransferase SDG725 2016a; Liu et al., 2017c; Ma et al., 2018). Ma et al. (2018) found modulates the expression of brassinosteroid (BR)-related genes, that DNA methylation levels, especially 24-nt siRNA-dependent including DWARF11 (D11), BRASSINOSTEROID INSENSITIVE 1 (BRI1) CHH methylation, were significantly reduced under HT stress in and BRASSINOSTEROID UPREGULATED 1(BU1), through mediating HT-sensitive cotton line compared to normal temperature (NT) the deposition of H3K36me2/3 on these genes. Li et al. (2018) re- condition, and experimental removal of DNA methylation led to ported that OsINO80, a conserved ATP-dependent chromatin- pollen sterility in HT-sensitive line under NT condition. They remodeling factor in rice, functions in the regulation of GA further proved that the suppression of DNA methylation affected biosynthesis. the expression of sugar and reactive oxygen species (ROS) pathway Recent studies also indicated that histone modifications are genes. Their work revealed a critical role of RdDM pathway in HT involved in the modulation of seed gene expression. Interest- stress. During salt stress response, Wang et al. (2014a) demon- ingly, although PcG complex and TrxG factors function antago- strated that induced DNA methylation changes occur in some nistically in flowering, a recent study reported that the PcG salinity-responsive genes in a salinity-tolerant wheat introgression 632 C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 line. Similarly, Xu et al. (2015) revealed that salt-induced tran- Fusarium oxysporum (Le et al., 2014). In plants, expression of scription factor MYB74 is regulated by RdDM pathway in Arabi- resistance (R) genes must be tightly controlled to balance plant dopsis. These findings suggest that a dynamic regulation of DNA growth and disease resistance. More recently, Dr. Zuhua He's group methylation is present in plant abiotic stress responses. identified a Pigm locus in rice which can confer durable resistance In plant stress responses, activation or repression of abiotic to the fungus Magnaporthe oryzae without yield penalty (Deng stress-responsive genes is often associated with multiple epige- et al., 2017). In this locus, PigmR confers broad-spectrum resis- netic changes. Besides DNA methylation, emerging evidence sug- tance, whereas PigmS represses resistance by competitively atten- gests that histone modifications are extensively involved in stress- uating PigmR homodimerization. Two tandem miniature responsive gene expression and gene priming in plants. Histone transposons (MITEs) are present in the promoter region of PigmS. modifier genes are differentially expressed upon exposure to These two MITEs are targeted by 24-nt siRNA-mediated RdDM abiotic stresses. For example, ATX1, the main H3K4 methyl- pathway and the expression of PigmS is regulated by DNA transferase in Arabidopsis, is involved in ABA-dependent and -in- methylation level in its promoter region. Silencing of RdDM dependent dehydration stress signaling pathways (Ding et al., pathway genes leads to increased PigmS expression. This finding 2011). Binding of ATX1 to NINE-CIS-EPOXYCAROTENOID DIOXYGE- strongly suggests that DNA methylation mechanism can modulate NASE 3 (NCED3), which encodes a key enzyme functioning in the plant immunity by affecting the expression of innate immunity ABA biosynthesis, is increased by dehydration stress, thereby receptor. increasing NCED3 transcription (Ding et al., 2011). Similarly, a Besides DNA methylation, recent studies demonstrated a close recent study reported that ATX4 and ATX5, the other two H3K4 link between the transcriptional levels of defense genes and his- methyltransferases in Arabidopsis, function partially redundantly to tone modifications. Among diverse histone modifications, histone modulate plant response to dehydration stress (Liu et al., 2018b). acetylation, which is dynamically regulated by histone acetyl- Loss-of-function single and double mutants of ATX4 and ATX5 transferases and deacetylases, is well-studied in plant immunity display drought stress-tolerant and ABA-hypersensitive pheno- (Zhou et al., 2005; Zhu et al., 2011; Ding et al., 2012). Zhou et al. types. Among the differentially expressed dehydration-responsive (2005) reported the important involvement of a histone deacety- genes caused by ATX4/ATX5 mutations, ABA-HYPERSENSITIVE lase, HDA19, in the transcriptional regulation of genes in jasmonic GERMINATION 3 (AHG3), which encodes a negative regulator of ABA acid (JA) and ethylene (ET) signaling defense pathways in Arabi- signaling, is directly bound by ATX4 and ATX5 for H3K4 methyl- dopsis. In this case, the expression of HDA19 is induced by pathogen ation, and this binding is dramatically increased upon ABA treat- Alternaria brassicicola and overexpression of HDA19 results in ment, suggesting a direct role of H3K4 methylation in dehydration decreased histone acetylation levels as well as increased resistance stress and ABA response. H3K4me3 demethylase JMJ15 is tissue- to A. brassicicola. Moreover, HDA19 has also been shown to interact specifically expressed in Arabidopsis and its loss-of-function with two type III WRKY transcription factors, WRKY38 and mutant displays more sensitive phenotype to salt stress (Shen WRKY62, to repress their transcription in basal defense responses et al., 2014). Ectopic expression of JMJ15 leads to mis-regulation (Kim et al., 2008). Similarly, histone deacetylase HDA6 serves as a of H3K4me2/3-dependent stress-responsive genes. In rice seed- corepressor of JASMONATE ZIM-DOMAIN (JAZ) proteins to repress lings, thousands of genes are differentially H3K4me3 modified ETHYLENE INSENSITIVE 3 (EIN3)/EIN3-LIKE 1 (EIL1)-dependent under drought stress (Zong et al., 2013). transcription, thereby inhibiting JA signaling defense pathway (Zhu Histone acetylation as an active histone mark also participates in et al., 2011). In addition, HDA6 also interacts with an F-box protein abiotic stress responses. It has been shown that HDA6- and HD2C- COI1 to modulate JA signaling defense (Devoto et al., 2002). In rice, mediated histone deacetylations are involved in ABA and salt stress evidence from Dr. Guo-Liang Wang's laboratory revealed that responses (Chen et al., 2010; Luo et al., 2012). In maize, histone HDT701, a histone deacetylase, negatively regulates plant innate deacetylase genes are induced by cold treatment (Hu et al., 2011). In immunity through modulating H4 acetylation of defense- rice, histone acetyltransferase genes are differently expressed upon responsive genes (Ding et al., 2012). In this case, HDT701 directly exposure to different abiotic stress treatments, including ABA, salt binds to defense-related genes. Silencing of HDT701 leads to and cold stresses (Liu et al., 2012b). Recent studies revealed an increased levels of H4 acetylation, elevated transcription of pattern involvement of ATP-dependent chromatin remodeling mechanism recognition receptor (PRR) and defense-related genes, as well as in abiotic stress responses. Han et al. (2012) reported that the SWI2/ enhanced resistance to both M. oryzae and Xanthomonas oryzae pv. SNF2 chromatin remodeling ATPase BRM regulates stress responses oryzae (Xoo). For histone methylation, ATXR7, a H3K4 methyl- through nucleosome stability of ABSCISIC ACID-INSENSITIVE5 (ABI5). transferase, associates with MODIFIER OF SNC1, 9 (MOS9) to In maize, the chromatin remodeler ZmCHB101 functions in osmotic regulate the transcriptional expression of R genes RECOGNITION OF stress response (Yu et al., 2018). PERONOSPORA PARASITICA 4 (RPP4) and SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1), thereby modulating the resistance to 7.2. Epigenetic regulation in plant immunity fungal pathogen Hyaloperonospora arabidopsidis Emwa1 (Xia et al., 2013). Dr. Dao-Xiu Zhou's laboratory proved that the histone In plants, perception of pathogens leads to the activation of demethylase JMJ705 is involved in the methyl JA-induced removal multiple layers of defense responses which are accompanied with of H3K27me3 and gene activation (Li et al., 2013). extensive transcriptional reprogramming of defense-responsive genes. Considering the advantages of rapid, reversible, even 8. Perspective transgenerational changes in gene expression, epigenetic mecha- nisms are very suitable for modulating plant defense responses. In this review, we summarize the advances in the field of plant However, these mechanisms have only recently attracted more epigenetics in China over the past several decades. We focus our attentions in plant defense immunity. review on the publications contributed by Chinese researchers and The important involvements of DNA methylation in biotic stress groups. Epigenetics, as the hotspot in the field of transcriptional responses were revealed by several recent observations that dys- regulation, has been developing rapidly over the past few decades. functions of DNA methyltransferases and demethylases lead to Benefiting from the growing funding and the importance of agri- different susceptibilities to certain pathogens, including bacterial cultural sciences, great achievements have been made in the field of pathogens (Dowen et al., 2012; Yu et al., 2013) and fungal pathogen plant epigenetics in China and some leading studies have been C.-G. Duan et al. / Journal of Genetics and Genomics 45 (2018) 621e638 633 emerging. With the constant discovery of novel epigenetic mech- Natural Science Foundation of China (No. 31770155). anisms and the elucidation of more and more crop genomes, epigenetic studies will undoubtedly continue to be a major focus of References study across biological disciplines. 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