Are Reprogramming Substrate Specificity of H4k12ac
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Genomic Analyses Reveal Foxg As an Upstream Regulator of Wnt1 Required For
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.08.416008; this version posted December 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Genomic analyses reveal FoxG as an upstream regulator of wnt1 required for posterior identity specification in planarians E. Pascual-Carreras1, M. Marín-Barba3, S. Castillo-Lara1, P. Coronel-Córdoba1, M.S. Magri2, G.N. Wheeler3 J.F. Abril1, J.L. Gomez-Skarmeta2, E. Saló1* & T. Adell1* 1 Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain. 2 Centro Andaluz de Biología del Desarollo (CABD), Universidad Pablo de Olavide, Sevilla, Spain. 3 School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK. *Corresponding authors: Emili Saló ([email protected]) and Teresa Adell ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.12.08.416008; this version posted December 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Embryonic specification of the first body axis requires the formation of an Organizer, a group of cells with the ability to instruct fates in the surrounding tissue. The existence of organizing regions in adults, i.e. -
Epigenetic Mechanisms of Lncrnas Binding to Protein in Carcinogenesis
cancers Review Epigenetic Mechanisms of LncRNAs Binding to Protein in Carcinogenesis Tae-Jin Shin, Kang-Hoon Lee and Je-Yoel Cho * Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea; [email protected] (T.-J.S.); [email protected] (K.-H.L.) * Correspondence: [email protected]; Tel.: +82-02-800-1268 Received: 21 September 2020; Accepted: 9 October 2020; Published: 11 October 2020 Simple Summary: The functional analysis of lncRNA, which has recently been investigated in various fields of biological research, is critical to understanding the delicate control of cells and the occurrence of diseases. The interaction between proteins and lncRNA, which has been found to be a major mechanism, has been reported to play an important role in cancer development and progress. This review thus organized the lncRNAs and related proteins involved in the cancer process, from carcinogenesis to metastasis and resistance to chemotherapy, to better understand cancer and to further develop new treatments for it. This will provide a new perspective on clinical cancer diagnosis, prognosis, and treatment. Abstract: Epigenetic dysregulation is an important feature for cancer initiation and progression. Long non-coding RNAs (lncRNAs) are transcripts that stably present as RNA forms with no translated protein and have lengths larger than 200 nucleotides. LncRNA can epigenetically regulate either oncogenes or tumor suppressor genes. Nowadays, the combined research of lncRNA plus protein analysis is gaining more attention. LncRNA controls gene expression directly by binding to transcription factors of target genes and indirectly by complexing with other proteins to bind to target proteins and cause protein degradation, reduced protein stability, or interference with the binding of other proteins. -
Bptf Is Essential for Murine Neocortical Development
Bptf is essential for murine neocortical development Gerardo Zapata Thesis submitted to the Faculty of Graduate and Postdoctoral Studies in partial fulfillment of the requirements for the Master’s degree in Biochemistry with specialization in Bioinformatics Department of Biochemistry, Microbiology and Immunology Faculty of Medicine University of Ottawa © Gerardo Zapata, Ottawa, Canada, 2020 Abstract Chromatin remodeling complexes modulate DNA accessibility permitting neuronal progenitor cells to proliferate and differentiate to form the mammalian neocortex. In the case of BPTF (Bromodomain PHD transcription Factor), the major subunit of a chromatin remodelling complex called NURF (Nucleosome Remodelling Factor), mutations leading to its haploinsufficiency have been linked to cause a recently annotated human neurodevelopmental disorder called NEDDFL (Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies). Patients with this syndrome are mainly characterized with microcephaly and intellectual disability. We conditionally knockout (cKO) the Bptf gene during neocortical neurogenesis to analyze its role during embryonic and postnatal brain development. The Bptf cKO animals reveal significant forebrain hypoplasia. During cortical neurogenesis, the Bptf cKO mice show a reduction in intermediate neuronal progenitor (INP) cells, an increase in apoptosis as well as a prolonged cell cycle within proliferating progenitors. Similarly, the postmitotic pyramidal neurons of the Bptf cKO mice contained lower levels of Ctip2 and Foxp1. Lastly, our RNA-seq analysis delineated gene pathways deregulated by Bptf removal, which are involved in neurogenesis and neuronal differentiation. Our results indicate that Bptf is critical for murine telencephalon neurogenesis. The hypoplasia demonstrated in the mouse model can resemble the microcephaly displayed by the human NEDDFL patients, highlighting the relevance of chromatin remodelling complexes during intricate neural developmental processes. -
Pointing the Finger
RESEARCH HIGHLIGHTS Nature Reviews Molecular Cell Biology | AOP, published online 14 June 2006; doi:10.1038/nrm1966 DOI: 10.1038/nrm1966 URLs BPTF http://ca.expasy.org/uniprot/ Q9UIG2 ING2 http://ca.expasy.org/uniprot/ Q9ESK4 GENE EXPRESSION Pointing the finger Mechanistic links between specific histone-tail tumour suppressors, bound specifically to modifications and their effects on gene H3K4me3. ING2 is a subunit of a SIN3a–HDAC1 expression have been difficult to establish. histone-deacetylase complex. The authors However, four papers in Nature now identify the showed that in response to DNA damage, binding plant homeodomain (PHD) finger as an important of the ING2 PHD finger to H3K4me3 that is effector domain that binds to the trimethylated present at the promoters of actively transcribed K4 residue of histone H3 (H3K4me3) and couples proliferation genes enhanced the association of it to gene activation in one case and to gene the ING2–HDAC1 complex at these genes. This repression in another. resulted in increased histone-deacetylase activity Wysocka et al. affinity purified the BPTF and hence acute repression of the cognate (bromodomain and PHD finger transcription transcript. These findings, together with those of factor) subunit of NURF — an ATP-dependent Wysocka et al., indicate that PHD fingers have a chromatin remodelling complex — using an general role as effector domains that link H3K4me3-containing peptide. Mutational analysis H3K4me3 to diverse biological outcomes. narrowed the H3K4me3-interaction region to the The molecular mechanism that underlies the second, conserved bromodomain-proximal PHD recognition of H3K4me3 by the PHD finger of finger of BPTF. Knockdown of the histone ING2 was reported in a fourth linked paper. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Role of Hmof-Dependent Histone H4 Lysine 16 Acetylation in the Maintenance of TMS1/ASC Gene Activity
Research Article Role of hMOF-Dependent Histone H4 Lysine 16 Acetylation in the Maintenance of TMS1/ASC Gene Activity Priya Kapoor-Vazirani, Jacob D. Kagey, Doris R. Powell, and Paula M. Vertino Department of Radiation Oncology and the Winship Cancer Institute, Emory University, Atlanta, Georgia Abstract occurring aberrantly during carcinogenesis, is associated with gene Epigenetic silencing of tumor suppressor genes in human inactivation (4). Histone modifications can also act synergistically cancers is associated with aberrant methylation of promoter or antagonistically to define the transcription state of genes. region CpG islands and local alterations in histone mod- Acetylation of histones H3 and H4 is associated with transcrip- ifications. However, the mechanisms that drive these events tionally active promoters and an open chromatin configuration (5). remain unclear. Here, we establish an important role for Both dimethylation and trimethylation of histone H3 lysine 4 histone H4 lysine 16 acetylation (H4K16Ac) and the histone (H3K4me2and H3K4me3) have been linked to actively transcribing acetyltransferase hMOF in the regulation of TMS1/ASC,a genes, although recent studies indicate that CpG island–associated proapoptotic gene that undergoes epigenetic silencing in promoters are marked by H3K4me2regardless of the transcrip- human cancers. In the unmethylated and active state, the tional status (6, 7). In contrast, methylation of histone H3 lysine 9 TMS1 CpG island is spanned by positioned nucleosomes and and 27 are associated with transcriptionally inactive promoters and marked by histone H3K4 methylation. H4K16Ac was uniquely condensed closed chromatin (8, 9). Interplay between histone localized to two sharp peaks that flanked the unmethylated modifications and DNA methylation defines the transcriptional CpG island and corresponded to strongly positioned nucle- potential of a particular chromatin domain. -
Bioinformatics Analysis for the Identification of Differentially Expressed Genes and Related Signaling Pathways in H
Bioinformatics analysis for the identification of differentially expressed genes and related signaling pathways in H. pylori-CagA transfected gastric cancer cells Dingyu Chen*, Chao Li, Yan Zhao, Jianjiang Zhou, Qinrong Wang and Yuan Xie* Key Laboratory of Endemic and Ethnic Diseases , Ministry of Education, Guizhou Medical University, Guiyang, China * These authors contributed equally to this work. ABSTRACT Aim. Helicobacter pylori cytotoxin-associated protein A (CagA) is an important vir- ulence factor known to induce gastric cancer development. However, the cause and the underlying molecular events of CagA induction remain unclear. Here, we applied integrated bioinformatics to identify the key genes involved in the process of CagA- induced gastric epithelial cell inflammation and can ceration to comprehend the potential molecular mechanisms involved. Materials and Methods. AGS cells were transected with pcDNA3.1 and pcDNA3.1::CagA for 24 h. The transfected cells were subjected to transcriptome sequencing to obtain the expressed genes. Differentially expressed genes (DEG) with adjusted P value < 0.05, | logFC |> 2 were screened, and the R package was applied for gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The differential gene protein–protein interaction (PPI) network was constructed using the STRING Cytoscape application, which conducted visual analysis to create the key function networks and identify the key genes. Next, the Submitted 20 August 2020 Kaplan–Meier plotter survival analysis tool was employed to analyze the survival of the Accepted 11 March 2021 key genes derived from the PPI network. Further analysis of the key gene expressions Published 15 April 2021 in gastric cancer and normal tissues were performed based on The Cancer Genome Corresponding author Atlas (TCGA) database and RT-qPCR verification. -
Histone Crosstalk Between H3s10ph and H4k16ac Generates a Histone Code That Mediates Transcription Elongation
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Histone Crosstalk between H3S10ph and H4K16ac Generates a Histone Code that Mediates Transcription Elongation Alessio Zippo,1 Riccardo Serafini,1 Marina Rocchigiani,1 Susanna Pennacchini,1 Anna Krepelova,1 and Salvatore Oliviero1,* 1Dipartimento di Biologia Molecolare Universita` di Siena, Via Fiorentina 1, 53100 Siena, Italy *Correspondence: [email protected] DOI 10.1016/j.cell.2009.07.031 SUMMARY which generates a different binding platform for the further recruitment of proteins that regulate gene expression. The phosphorylation of the serine 10 at histone H3 In Drosophila it has been shown that H3S10ph is required for has been shown to be important for transcriptional the recruitment of the positive transcription elongation factor activation. Here, we report the molecular mechanism b (P-TEFb) on the heat shock genes (Ivaldi et al., 2007) although through which H3S10ph triggers transcript elonga- these results have been challenged (Cai et al., 2008). tion of the FOSL1 gene. Serum stimulation induces In mammalian cells, nucleosome phosphorylation localized at the PIM1 kinase to phosphorylate the preacetylated promoters has been directly linked with transcriptional activa- tion. It has been shown that H3S10ph enhances the recruitment histone H3 at the FOSL1 enhancer. The adaptor of GCN5, which acetylates K14 on the same histone tail (Agalioti protein 14-3-3 binds the phosphorylated nucleo- et al., 2002; Cheung et al., 2000). Steroid hormone induces the some and recruits the histone acetyltransferase transcriptional activation of the MMLTV promoter by activating MOF, which triggers the acetylation of histone H4 MSK1 that phosphorylates H3S10, leading to HP1g displace- at lysine 16 (H4K16ac). -
The ISWI Chromatin Remodelling Factor NURF Is Not Required for Mitotic
1/26/2021 - Open Access The ISWI chromatin remodelling factor NURF is not required for mitotic male X chromosome organisation So Yeon Kwon1§*, Boyun Jang1* and Paul Badenhorst1§ 1Birmingham Centre for Genome Biology and Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, United Kingdom §To whom correspondence should be addressed: [email protected]; [email protected] *These authors contributed equally. Abstract The nucleosome remodelling factor (NURF) is an ISWI-class ATP-dependent chromatin remodeling enzyme required both for gene expression and higher order chromatin organisation. NURF binds to histone modifications that decorate the Drosophila polytene male X chromosome and is required to maintain correct organisation of this chromosome. NURF mutants exhibit distorted and decondensed polytene male X chromosomes dependent on the presence of the male-specific lethal (MSL) complex. Here we tested whether mitotic chromosomes similarly require NURF to maintain correct morphology. Surprisingly, although the MSL complex remains associated with mitotic male X chromosomes, NURF is not required to maintain morphology. While the ISWI subunit of NURF is known to remain associated with mitotic chromosomes we show that the NURF specificity subunit Nurf301/BPTF dissociates from chromatin during both Drosophila and human mitosis, further illuminating that NURF is dispensable for mitotic chromosome organisation. Figure 1. The chromatin remodelling factor NURF is not required for mitotic chromosome cohesion, condensation or X chromosome morphology: A) Mutation of either the NURF specificity subunit Nurf301 or the NURF catalytic subunit Iswi does not disrupt male X chromosome morphology or result in loss of sister chromatid cohesion. -
HIRA Orchestrates a Dynamic Chromatin Landscape in Senescence and Is Required for Suppression of Neoplasia
Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia Taranjit Singh Rai,1,2,3 John J. Cole,1,2,5 David M. Nelson,1,2,5 Dina Dikovskaya,1,2 William J. Faller,1 Maria Grazia Vizioli,1,2 Rachael N. Hewitt,1,2 Orchi Anannya,1 Tony McBryan,1,2 Indrani Manoharan,1,2 John van Tuyn,1,2 Nicholas Morrice,1 Nikolay A. Pchelintsev,1,2 Andre Ivanov,1,2,4 Claire Brock,1,2 Mark E. Drotar,1,2 Colin Nixon,1 William Clark,1 Owen J. Sansom,1 Kurt I. Anderson,1 Ayala King,1 Karen Blyth,1 and Peter D. Adams1,2 1Beatson Institute for Cancer Research, Bearsden, Glasgow G61 1BD, United Kingdom; 2Institute of Cancer Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G61 1BD, United Kingdom; 3Institute of Biomedical and Environmental Health Research, University of West of Scotland, Paisley PA1 2BE, United Kingdom Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. -
Molecular Mechanisms Regulating Lifespan and Environmental Stress Responses Saya Kishimoto1,2, Masaharu Uno1,2 and Eisuke Nishida1,2*
Kishimoto et al. Inflammation and Regeneration (2018) 38:22 Inflammation and Regeneration https://doi.org/10.1186/s41232-018-0080-y REVIEW Open Access Molecular mechanisms regulating lifespan and environmental stress responses Saya Kishimoto1,2, Masaharu Uno1,2 and Eisuke Nishida1,2* Abstract Throughout life, organisms are subjected to a variety of environmental perturbations, including temperature, nutrient conditions, and chemical agents. Exposure to external signals induces diverse changes in the physiological conditions of organisms. Genetically identical individuals exhibit highly phenotypic variations, which suggest that environmental variations among individuals can affect their phenotypes in a cumulative and inhomogeneous manner. The organismal phenotypes mediated by environmental conditions involve development, metabolic pathways, fertility, pathological processes, and even lifespan. It is clear that genetic factors influence the lifespan of organisms. Likewise, it is now increasingly recognized that environmental factors also have a large impact on the regulation of aging. Multiple studies have reported on the contribution of epigenetic signatures to the long-lasting phenotypic effects induced by environmental signals. Nevertheless, the mechanism of how environmental stimuli induce epigenetic changes at specific loci, which ultimately elicit phenotypic variations, is still largely unknown. Intriguingly, in some cases, the altered phenotypes associated with epigenetic changes could be stably passed on to the next generations. In this review, we discuss the environmental regulation of organismal viability, that is, longevity and stress resistance, and the relationship between this regulation and epigenetic factors, focusing on studies in the nematode C. elegans. Keywords: Aging, Lifespan extension, Environmental factor, Stress response, Epigenetics, Transgenerational inheritance Background actively controlled process that is conserved across spe- Aging is an inevitable event for most living organisms cies, from yeast to mammals. -
Transcription Shapes Genome-Wide Histone Acetylation Patterns
ARTICLE https://doi.org/10.1038/s41467-020-20543-z OPEN Transcription shapes genome-wide histone acetylation patterns Benjamin J. E. Martin 1, Julie Brind’Amour 2, Anastasia Kuzmin1, Kristoffer N. Jensen2, Zhen Cheng Liu1, ✉ Matthew Lorincz 2 & LeAnn J. Howe 1 Histone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. 1234567890():,; Using immunoblot and chromatin immunoprecipitation-sequencing in S. cerevisiae, here we show that the majority of histone acetylation is dependent on transcription. This dependency is partially explained by the requirement of RNA polymerase II (RNAPII) for the interaction of H4 histone acetyltransferases (HATs) with gene bodies. Our data also confirms the targeting of HATs by transcription activators, but interestingly, promoter-bound HATs are unable to acetylate histones in the absence of transcription. Indeed, HAT occupancy alone poorly predicts histone acetylation genome-wide, suggesting that HAT activity is regulated post- recruitment. Consistent with this, we show that histone acetylation increases at nucleosomes predicted to stall RNAPII, supporting the hypothesis that this modification is dependent on nucleosome disruption during transcription. Collectively, these data show that histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases. 1 Department of Biochemistry and Molecular Biology, Life Sciences Institute, Molecular