DOCSLIB.ORG

Heterochromatin Protects Retinal Pigment Epithelium Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Heterochromatin Protects Retinal Pigment Epithelium Cells Heterochromatin protects retinal pigment epithelium PNAS PLUS cells from oxidative damage by silencing p53 target genes Lili Gonga,1,2, Fangyuan Liua,1, Zhen Xionga,1, Ruili Qia,1, Zhongwen Luoa,1, Xiaodong Gonga, Qian Niea,b, Qian Suna, Yun-Fei Liua, Wenjie Qinga,b, Ling Wanga,b,c, Lan Zhanga, Xiangcheng Tanga, Shan Huanga, Gen Lia, Hong Ouyanga, Mengqing Xianga,d,e, Quan Dong Nguyenf, Yizhi Liua,2, and David Wan-Cheng Lia,b,c,2 aState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060 Guangdong, China; bKey Laboratory of Protein Chemistry and Developmental Biology, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China; cTruhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE 68198; dCenter for Advanced Biotechnology and Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854; eDepartment of Pediatrics, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854; and fByers Eye Institute, Stanford University School of Medicine, Palo Alto, CA 94303 Edited by Michael Karin, University of California San Diego School of Medicine, La Jolla, CA, and approved February 20, 2018 (received for review September 6, 2017) Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell thought to be maintained in a transcriptionally silenced state by apoptosis is critically implicated in the pathogenesis of age-related the repressive H3K9me3 mark; however, aberrant satellite macular degeneration (AMD), a leading cause of blindness in the transcription can cause heterochromatin disorganization and elderly. Heterochromatin, a compact and transcriptional inert chro- genome instability, which have been linked to carcinogenesis (8, matin structure, has been recently shown to be dynamically regu- 9). We and others have recently found that repression of satellite lated in response to stress stimuli. The functional mechanism of is a critical mechanism by which tumor suppressors protect ge- heterochromatin on OS exposure is unclear, however. Here we show nome stability (8, 10). that OS increases heterochromatin formation both in vivo and in The H3K9me3 mark has been detected on p53-regulated gene vitro, which is essential for protecting RPE cells from oxidative promoters, which can be abrogated on p53 activation by MDM2- damage. Mechanistically, OS-induced heterochromatin selectively mediated SUV39H1 degradation (11, 12). How ubiquitously accumulates at p53-regulated proapoptotic target promoters and distributed heterochromatin accumulates at specific p53 target inhibits their transcription. Furthermore, OS-induced desumoylation loci and mediates stress response is currently unknown, however. – of p53 promotes p53 heterochromatin interaction and regulates The interaction of p53 with chromatin is tightly regulated by its p53 promoter selection, resulting in the locus-specific recruitment posttranslational medications, among which sumoylation has of heterochromatin and transcription repression. Together, our find- been shown to prevent p53 binding to DNA in vitro (13). Nev- ings demonstrate a protective function of OS-induced heterochroma- ertheless, the function of p53 sumoylation in vivo is largely un- tin formation in which p53 desumoylation-guided promoter selection defined, as both activation and inhibition of its downstream gene and subsequent heterochromatin recruitment play a critical role. We transcription were observed (13–15). propose that targeting heterochromatin provides a plausible thera- peutic strategy for the treatment of AMD. Significance age-related macular degeneration | oxidative stress | RPE | heterochromatin | p53 Oxidative stress-induced damage to retinal pigmented epithelial (RPE) cells is critically implicated in the pathogenesis of age- related macular degeneration (AMD), a leading cause of blind- CELL BIOLOGY he retinal pigment epithelium (RPE) is the pigmented cell ness in the elderly. Here we report that oxidative stress-induced layer of the retina that supports and nourishes photorecep- T heterochromatin formation is essential to promote RPE survival. tors (1). Because of the intense illumination from focal light, the Mechanistically, oxidative damage-induced formation of het- high oxygen tension in the macular area, and the phagocytosis of erochromatin occurs at the 53 target promoters of apoptosis photoreceptor outer segments, RPE cells are particularly sensi- genes and is regulated by p53 sumoylation. Our study demon- tive to oxidative stress (OS). Strong evidence supports the hy- strates mechanistic links among chromatin conformation, p53 pothesis that cumulative OS-induced RPE apoptosis is a major sumoylation, and RPE cell death. We propose that targeting factor in the etiology of age-related macular degeneration heterochromatin provides a novel strategy for AMD treatment. (AMD), the primary cause of blindness in elderly persons (2, 3). Although OS-induced gene regulation in RPE cells has been well Author contributions: L.G., Y.L., and D.W.-C.L. designed research; L.G., F.L., Z.X., R.Q., Z.L., studied, little is known about the functions of gene-poor het- X.G., Q.N., Q.S., Y.-F.L., W.Q., L.W., X.T., and S.H. performed research; L.Z., G.L., and H.O. erochromatin during this process. In fact, heterochromatin, contributed new reagents/analytic tools; L.G., M.X., Q.D.N., Y.L., and D.W.-C.L. analyzed data; and L.G., Y.L., and D.W.-C.L. wrote the paper. which is generally associated with the maintenance of gene si- The authors declare no conflict of interest. lencing, is also dynamically regulated in response to stress (4). Chromatin is divided into euchromatin and heterochromatin This article is a PNAS Direct Submission. based on differential compaction during interphase, with het- This open access article is distributed under Creative Commons Attribution-NonCommercial- NoDerivatives License 4.0 (CC BY-NC-ND). erochromatin being highly condensed, existing in transcriptional Data deposition: The ChIP-seq data have been deposited into NCBI-SRA database (acces- inert conformation (5). Heterochromatin is generated and sion no. SRP132687). maintained by epigenetic modifications, mainly trimethylation of 1L.G., F.L., Z.X., R.Q., and Z.L. contributed equally to this work. histone 3 lysine 9 (H3K9me3), in which suppressor of variegation 2To whom correspondence may be addressed. Email: [email protected], gonglili@ 3–9 homolog 1 (Drosophila) (SUV39H1) is the principle meth- mail.sysu.edu.cn, or [email protected]. yltransferase (6). Embedded within heterochromatin is a group This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. of highly repetitive DNA sequences, known as satellite DNAs, 1073/pnas.1715237115/-/DCSupplemental. that give rise to noncoding satellite RNAs (7). Satellite DNA is Published online April 5, 2018. www.pnas.org/cgi/doi/10.1073/pnas.1715237115 PNAS | vol. 115 | no. 17 | E3987–E3995 Downloaded by guest on September 26, 2021 In the present study, we used mouse models and cultured human matin functionally silenced satellite transcription both in vitro RPE cells to investigate the functional mechanism of heterochro- and in vivo. matin on OS exposure. We found that OS-induced heterochro- matin formation occurs both in vitro and in vivo. Pharmaceutical Heterochromatin Is Needed to Protect RPE from OS-Induced Apoptosis. and genetic approaches demonstrated that the formation of het- To determine the biological functions of OS-induced hetero- erochromatin was essential for the survival of OS-exposed RPE chromatin formation, we first treated mice by oral gavage with cells. Mechanistically, the OS-induced H3K9me3 heterochromatin vehicle control or chaetocin, a selective inhibitor of SUV39 on p53 target promoters silenced the transcription of p53-dependent methyltransferases that methylate H3K9 (20). Chaetocin alone apoptotic genes, which was regulated by the desumoylation of p53. had no obvious effect on RPE morphology; however, chaetocin Together, our results present a mechanism regulating the interaction treatment dramatically sensitized RPE cells to OS, leading to between p53 and heterochromatin during OS exposure, which has a disruption of the RPE structure under low levels of NaIO3 and previously unknown protective function. marked RPE degeneration at higher dosages (Fig. 2A). We next assessed the effects of chaetocin on hRPE cells. Similar to the Results effects observed in mouse RPE, exposure to chaetocin alone did OS Increases Heterochromatin Formation in RPE Cells. To ascertain not affect hRPE cell viability, but it did increase apoptosis in OS- RPE heterochromatin status on OS exposure, mice were injected exposed cells (Fig. 2B). Overexpression of satellite transcripts is a with sodium iodate (NaIO3), a stable oxidizing agent that targets hallmark of heterochromatin destabilization; thus, we transfected primarily the RPE (16). Consistent with previous reports, NaIO3 human and mouse satellite into hRPE cells, and detected in- injection led to significant thinning of the retina and disruption creased apoptosis also in satellite-overexpressing cells on OS ex- of the RPE structure (Fig. 1 A and B). Interestingly, we observed posure (Fig. 2C and Fig. S3). Together, these results suggest that dramatically increased H3K9me3 immunofluorescence (IF) sig- heterochromatin maintenance is required for RPE survival upon nals in RPE cells on OS exposure (Fig. 1 B, a). The number of OS exposure. H3K9me3-positive RPE cells was increased by approximately We
Load more

Recommended publications
  • The Basic Karyotype of Rye Giemsa and Fluorescence
    Heredity (1974) 33 (3), 403-408 THEBASIC KARYOTYPE OF RYE (SECALE CEREALE) ANALYSED WITH GIEMSA AND FLUORESCENCE METHODS CANIO G. VOSA Botany School, Oxford Received26.iii.74 SUMMARY The basic karyotype of Rye (Secale cereale L.) has been analysed with several fluorochromes and with a Giemsa staining technique. Only the fluoro- chrome Hoechst 33258 and the Giemsa technique were successful in differenti- ating the heterochromatic segments. Five cultivated varieties were studied. In the haploid set there are 11 large and two small terminally located bands, four small intercalary bands and a variable band adjacent to the nucleolar constriction on chromosome VII which are constant for all varieties. Five more very small intercalary bands occur sporadically in all the varieties. All the chromosomes possess thin centromeric bands. 1. INTRODUCTION RYE is the hardiest of the cereals and its cultivation reaches beyond the Arctic Circle. It is of considerable importance in Russia, Sweden, Poland, the Netherlands and Belgium. In Britain, Rye has ceased to be of any great importance since the change to wheaten bread in the eighteenth century. Compared with other cereals, Rye has fewer varieties and these are not very uniform because of cross-pollination which is the rule in Rye but the exception in other cereal crops. It probably occurred as a weed in fields before being accepted as a crop rather later in the history of civilisation.Its oldest archaeological records date from the first Iron Age (Halstatt period, c. 900-700 B.C.). Thefirst chromosome counts are those of Nemec (1910) as cited by Emme (1928), giving 18 chromosomes for endosperm cells.
    [Show full text]
  • Extra Euchromatic Band in the Qh Region of Chromosome 9
    J Med Genet: first published as 10.1136/jmg.22.2.156 on 1 April 1985. Downloaded from 156 Short reports two centromeres indicated by two distinct C bands but only I HANCKE AND K MILLER one primary constriction at the proximal C band. The two Department of Human Genetics, C bands were separated by chromosomal material staining Medizinische Hochschule Hannover, pale in G banding and intensely dark in R banding (fig 1). Hannover, Both NORs could be observed in satellite associations (fig Federal Republic of Germany. 2). The chromosome was therefore defined as pseudo- dicentric chromosome 21 (pseudic 21). The same chromo- References some was found in the proband's father and paternal Balicek P, Zizka, J. Intercalar satellites of human acrocentric grandmother. chromosomes as a cytological manifestation of polymorphisms Acrocentric chromosomes with a short arm morphology in GC-rich material? Hum Genet 1980;54:343-7. similar to that presented here have been reported by 2 Ing PS, Smith SD. Cytogenetic studies of a patient with Balicek and Zizka.' These authors paid no attention to the mosaicism of isochromosome 13q and a dicentric (Y;13) activity of the centromeres. The suppression of additional translocation showing differential centromeric activity. Clin centromeres is indicated by the presence of only one Genet 1983;24:194-9. primary constriction as shown by Ing and Smith2 in a 3 Passarge E. Analysis of chromosomes in mitosis and evaluation dicentric (Y;13) transtocation. Variants of acrocentric of cytogenetic data. 5. Variability of the karyotype. In: Schwarzacher HG, Wolf U, eds. Methods in human cytogene- chromosomes are often observed in patients with congen- tics.
    [Show full text]
  • Repetitive Elements in Humans
    International Journal of Molecular Sciences Review Repetitive Elements in Humans Thomas Liehr Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, D-07747 Jena, Germany; [email protected] Abstract: Repetitive DNA in humans is still widely considered to be meaningless, and variations within this part of the genome are generally considered to be harmless to the carrier. In contrast, for euchromatic variation, one becomes more careful in classifying inter-individual differences as meaningless and rather tends to see them as possible influencers of the so-called ‘genetic background’, being able to at least potentially influence disease susceptibilities. Here, the known ‘bad boys’ among repetitive DNAs are reviewed. Variable numbers of tandem repeats (VNTRs = micro- and minisatellites), small-scale repetitive elements (SSREs) and even chromosomal heteromorphisms (CHs) may therefore have direct or indirect influences on human diseases and susceptibilities. Summarizing this specific aspect here for the first time should contribute to stimulating more research on human repetitive DNA. It should also become clear that these kinds of studies must be done at all available levels of resolution, i.e., from the base pair to chromosomal level and, importantly, the epigenetic level, as well. Keywords: variable numbers of tandem repeats (VNTRs); microsatellites; minisatellites; small-scale repetitive elements (SSREs); chromosomal heteromorphisms (CHs); higher-order repeat (HOR); retroviral DNA 1. Introduction Citation: Liehr, T. Repetitive In humans, like in other higher species, the genome of one individual never looks 100% Elements in Humans. Int. J. Mol. Sci. alike to another one [1], even among those of the same gender or between monozygotic 2021, 22, 2072.
    [Show full text]
  • Sir2 Mitigates an Intrinsic Imbalance in Origin Licensing Efficiency Between Early- and Late-Replicating Euchromatin
    Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- and late-replicating euchromatin Timothy Hoggarda, Carolin A. Müllerb, Conrad A. Nieduszynskib, Michael Weinreichc, and Catherine A. Foxa,1 aDepartment of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53706; bSir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, United Kingdom; and cDivision of Molecular and Cellular Biosciences, National Science Foundation, Alexandria, VA 22314 Edited by Jasper Rine, University of California, Berkeley, CA, and approved May 7, 2020 (received for review March 11, 2020) A eukaryotic chromosome relies on the function of multiple illuminate issues relevant to genome replication that would be spatially distributed DNA replication origins for its stable inheri- difficult to glean from classical approaches. It is now established tance. The spatial location of an origin is determined by the that approximately half of yeast origins, distributed broadly over chromosomal position of an MCM complex, the inactive form of the the central regions of chromosomes, act in the first portion of S DNA replicative helicase that is assembled onto DNA in G1-phase phase (early and mid origins), while the remaining origins, gen- (also known as origin licensing). While the biochemistry of origin erally located between ∼15 and 75 kb from the telomeric ends, licensing is understood, the mechanisms that promote an adequate act later (late origins). Most of the yeast genome is euchromatic, spatial distribution of MCM complexes across chromosomes are not. and its duplication requires both early and late origins (Fig. 1). We have elucidated a role for the Sir2 histone deacetylase in estab- The terminal 5 to 10 kb of yeast chromosomes exist in a het- lishing the normal distribution of MCM complexes across Saccharo- erochromatic structure.
    [Show full text]
  • Transcription Organizes Euchromatin Via Microphase Separation
    ARTICLE https://doi.org/10.1038/s41467-021-21589-3 OPEN Transcription organizes euchromatin via microphase separation Lennart Hilbert 1,2,3,7,8, Yuko Sato4,11, Ksenia Kuznetsova2,11, Tommaso Bianucci 2,3,11, Hiroshi Kimura 4, ✉ Frank Jülicher 1,3,5,6, Alf Honigmann2, Vasily Zaburdaev1,3,9,12 & Nadine L. Vastenhouw 2,10,12 In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for tran- 1234567890():,; scription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. While transcription and RNA have been implicated in euchromatin organization, it remains unclear how their interplay forms and maintains tran- scription pockets. Here we combine theory and experiment to analyze the dynamics of euchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription. We show that accumulation of RNA induces formation of transcription pockets which dis- place transcriptionally inactive chromatin. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchro- matin. Full phase separation is prevented because RNA remains tethered to transcribed euchromatin through RNA polymerases. Instead, smaller scale microphases emerge that do not grow further and form the typical pattern of euchromatin organization. 1 Center for Systems Biology Dresden, Dresden, Germany. 2 Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. 3 Max Planck Institute for the Physics of Complex Systems, Dresden, Germany. 4 Tokyo Institute of Technology, Yokohama, Kanagawa, Japan. 5 Center for Advancing Electronics Dresden, Technical University Dresden, Dresden, Germany.
    [Show full text]
  • Condensed DNA: Condensing the Concepts
    Progress in Biophysics and Molecular Biology 105 (2011) 208e222 Contents lists available at ScienceDirect Progress in Biophysics and Molecular Biology journal homepage: www.elsevier.com/locate/pbiomolbio Review Condensed DNA: Condensing the concepts Vladimir B. Teif a,b,*, Klemen Bohinc c,d a BioQuant and German Cancer Research Center, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany b Institute of Bioorganic Chemistry, Belarus National Academy of Sciences, Kuprevich 5/2, 220141, Minsk, Belarus c Faculty of Health Sciences, Zdravstvena pot 5, 1000 Ljubljana, Slovenia d Faculty of Electrical Engineering, University of Ljubljana, Trzaska 25, 1000 Ljubljana, Slovenia article info abstract Article history: DNA is stored in vivo in a highly compact, so-called condensed phase, where gene regulatory processes Available online 16 July 2010 are governed by the intricate interplay between different states of DNA compaction. These systems often have surprising properties, which one would not predict from classical concepts of dilute solutions. The Keywords: mechanistic details of DNA packing are essential for its functioning, as revealed by the recent devel- DNA condensation opments coming from biochemistry, electrostatics, statistical mechanics, and molecular and cell biology. Ligand binding Different aspects of condensed DNA behavior are linked to each other, but the links are often hidden in Counterion correlations the bulk of experimental and theoretical details. Here we try to condense some of these concepts and Macromolecular crowding fi Chromatin provide interconnections between the different elds. After a brief description of main experimental Gene regulation features of DNA condensation inside viruses, bacteria, eukaryotes and the test tube, main theoretical approaches for the description of these systems are presented.
    [Show full text]
  • Mitochondrial Stability in Diabetic Retinopathy: Lessons Learned from Epigenetics
    Diabetes Volume 68, February 2019 241 Mitochondrial Stability in Diabetic Retinopathy: Lessons Learned From Epigenetics Renu A. Kowluru Diabetes 2019;68:241–247 | https://doi.org/10.2337/dbi18-0016 Diabetic retinopathy remains the leading cause of ac- With time, preretinal hemorrhage and neovascularization quired blindness in working-age adults. While the cutting- begin to appear, and if not treated, the retina detaches, edge research in the field has identified many leading to blindness. The pathogenesis of the disease is molecular, functional, and structural abnormalities, the strongly associated with the duration of diabetes, and exact molecular mechanism of this devastating disease uncontrolled blood glucose is considered as the primary remains obscure. Diabetic environment drives dysfunc- driving factor; however, blood pressure and hyperlipid- tion of the power generator of the cell and disturbs the emia also play significant roles in its development. Although PERSPECTIVES IN DIABETES homeostasis of mitochondrial dynamic. Mitochondrial the clinical pathology of diabetic retinopathy is mainly DNA (mtDNA) is damaged, the transcription of mtDNA- observed in the retinal microvasculature, recent evidence encoded genes is impaired, and the electron transport has clearly demonstrated neurodegeneration as an early chain is compromised, fueling into a vicious cycle of free event in the pathogenesis of this blinding disease (2,3). radicals. The hyperglycemic milieu also alters the epige- High glucose initiates a whole array of molecular, bio- netic machinery, and mtDNA and other genes associated with mitochondrial homeostasis are epigenetically mod- chemical, and functional abnormalities affecting many ified, further contributing to the mitochondrial damage. metabolic pathways including activation of protein kinase Thus, mitochondria appear to have a significant role in C, increased production of advanced glycation end prod- the development of diabetic retinopathy, and unravel- ucts, and polyol and hexosamine pathways.
    [Show full text]
  • Supernumerary Chromosome 8 FTNW
    Supernumerary chromosome 8 rarechromo.org Supernumerary chromosome 8 Supernumerary chromosome 8 means that there is a tiny extra part of a chromosome in all or some of the cells of the body. In addition to the 46 chromosomes that everyone has, people with a supernumerary chromosome 8 have a small extra chromosome made from chromosome 8 material. The small extra chromosome can have different possible shapes. It can also have different names. The most common names are: small supernumerary marker chromosome (sSMC ) supernumerary ring chromosome (SRC ), if it’s in the form of a ring Other names you might find in the medical literature include: small accessory chromosome (SAC ) extra structurally abnormal chromosome (ESAC ). Genes and chromosomes Our bodies are made up of billions of cells. Most of the cells contain a complete set of tens of thousands of genes which act like a set of instructions, controlling our growth and development and how our bodies work. Genes are carried on microscopically small, thread-like structures called chromosomes. There are usually 46 chromosomes, 23 inherited from our mother and 23 inherited from our father, so we have two sets of 23 chromosomes in ‘pairs’. Apart from two sex chromosomes (two Xs for a girl and an X and a Y for a boy) the chromosomes are numbered 1 to 22, generally from largest to smallest. Sources & references The information in this leaflet is drawn partly from published medical research where there are reports of around 40 cases. The first-named author and publication date are given to allow you to look for the abstracts or original articles on the internet in PubMed (at www.ncbi.nlm/ nih.gov/pubmed ).
    [Show full text]
  • Primates: Cebidae) Mariela Nieves1,2*, María Isabel Remis2,3, Carla Sesarini1, Diana Lucrecia Hassel4, Carina Francisca Argüelles4 & Marta Dolores Mudry1,2
    www.nature.com/scientificreports OPEN Assessment of genetic variability in captive capuchin monkeys (Primates: Cebidae) Mariela Nieves1,2*, María Isabel Remis2,3, Carla Sesarini1, Diana Lucrecia Hassel4, Carina Francisca Argüelles4 & Marta Dolores Mudry1,2 Capuchin monkeys (genera Cebus and Sapajus) show a wide range distribution, from Honduras to Argentina. The aim of this work was to evaluate the genetic and phenotypic variability of captive specimens putatively belonging to S. cay (SCY) and S. nigritus (SNI) at their southernmost distribution limit. Forty-four individuals held in fve captive centers from Argentina were analyzed based on external morphology, karyology and DNA sequences of mitochondrial control region (mtDNA-CR). Three morphotypes associated with their probable geographical origin in SCY and a single morphotype in SNI were found. For SCY we could associate each morphotype with the most frequent karyotype. SNI showed a single phenotype and a homogenous karyotype. Heterochromatin showed geographical patterns within species. A 515-bp mtDNA-CR fragment was sequenced, defning fourteen haplotypes at 59 polymorphic sites. A network constructed with our 14 haplotypes and other 77 from S. apella, S. macrocephalus, S. cay and S. nigritus from bibliography revealed some phylogeographic signals. Our SCY and SNI samples rendered four groups that difered in multiple mutational steps, with SCY being more similar to S. apella than to S. macrocephalus. Also, we identifed two genetic divergent SCY groups: samples from NOA and from NEA with high mitochondrial diversity. Our results highlight the relevance of using complementary genetic tools throughout the distribution ranges of SCY and SNI for a better assessment of their diversity.
    [Show full text]
  • Euchromatin and Pericentromeric Heterochromatin: Comparative Composition in the Tomato Genome
    Copyright Ó 2006 by the Genetics Society of America DOI: 10.1534/genetics.106.055772 Euchromatin and Pericentromeric Heterochromatin: Comparative Composition in the Tomato Genome Ying Wang,*,†,1 Xiaomin Tang,‡ Zhukuan Cheng,‡ Lukas Mueller,*,† Jim Giovannoni§,** and Steve D. Tanksley*,†,2 *Department of Plant Breeding and Genetics, †Department of Plant Biology, §Boyce Thompson Institute for Plant Research and **U.S. Department of Agriculture–Agricultural Research Service, Plant, Soil, and Nutrition Lab, Cornell University, Ithaca, New York 14853 and ‡Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China Manuscript received October 18, 2005 Accepted for publication February 6, 2006 ABSTRACT Eleven sequenced BACs were annotated and localized via FISH to tomato pachytene chromosomes providing the first global insights into the compositional differences of euchromatin and pericentromeric heterochromatin in this model dicot species. The results indicate that tomato euchromatin has a gene density (6.7 kb/gene) similar to that of Arabidopsis and rice. Thus, while the euchromatin comprises only 25% of the tomato nuclear DNA, it is sufficient to account for 90% of the estimated 38,000 non- transposon genes that compose the tomato genome. Moreover, euchromatic BACs were largely devoid of transposons or other repetitive elements. In contrast, BACs assigned to the pericentromeric hetero- chromatin had a gene density 10–100 times lower than that of the euchromatin and are heavily populated by retrotransposons preferential to the heterochromatin—the most abundant transposons belonging to the Jinling Ty3/gypsy-like retrotransposon family. Jinling elements are highly methylated and rarely transcribed. Nonetheless, they have spread throughout the pericentromeric heterochromatin in tomato and wild tomato species fairly recently—well after tomato diverged from potato and other related sola- naceous species.
    [Show full text]
  • CENP-B Dynamics at Centromeres Is Regulated by a Sumoylation
    bioRxiv preprint doi: https://doi.org/10.1101/245597; this version posted January 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 CENP-B dynamics at centromeres is regulated by a SUMOylation/ubiquitination and 2 proteasomal-dependent degradation mechanism involving the SUMO-targeted ubiquitin E3 3 ligase RNF4 4 Jhony El Maalouf 1,, Pascale Texier 1,4, Indri Erliandri 1,4, Camille Cohen 1, Armelle Corpet 1, Frédéric 5 Catez 2, Chris Boutell 3, Patrick Lomonte 1,* 6 7 1. Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, 8 Institut NeuroMyoGène (INMG), team Chromatin Assembly, Nuclear Domains, Virus. F-69100, Lyon, 9 France 10 2. Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5286, INSERM U 1052, Centre de 11 Recherche en Cancérologie de Lyon. F-69000, Lyon, France 12 3. MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland (UK) 13 4. Contributed equally to this work. 14 15 * Corresponding author: [email protected] 16 17 18 Running title: SUMO & ubiquitin-dependent CENP-B dynamics 19 20 Word count: 6743 21 22 23 24 The English of parts of this document has been checked by at least two professional editors, both native 25 speakers of English. For a certificate, please see: 26 27 http://www.textcheck.com/certificate/gh7EcX 28 29 30 1 bioRxiv preprint doi: https://doi.org/10.1101/245597; this version posted January 9, 2018.
    [Show full text]
  • Does Histone Modification Affect Euchromatin
    Does Histone Modification Affect Euchromatin exsanguinatingIs Jeremias unmarketable his serenata. when Dominick Lawrence segue unhedged dogmatically. desperately? Recommended and pug-nosed Federico always knife unwarily and The euchromatin given that involved, does not clear how epigenetic regulation during dna can promote gene regulation during gestation. Treatment of mammalian cells with histone deacetylase inhibitors to increase euchromatin or histone transferase inhibitors to decrease heterochromatin results in a soft nucleus and nuclear blebbing, without perturbing lamins. These units are likely built up from smaller loop domains. Acetylation of histone H3 at lysine 64 regulates nucleosome. Whereas cells of metazoan origin are then lysed directly, yeast cells must first undergo cell wall breakage, which can be accomplished by either mechanical shearing or enzymatic digestion. To spike if microorganisms were available of modifying plutonium form the soil. Histone modifications in Arabidopsis high methylation of H3 lysine Kaposi virus. How do cells divide? Loss of DNA methylation leads to activation of normally silenced DNA sequences like the transposable elements. Cusabio technology llc all prices are generally transcriptionally active state to be cooperation between histone ptms addition, does histone modification affect euchromatin or which is wrapped into chromatin modifications. The epigenome profiling identifies histone modification levels can think that facilitates transcription from sam as a large blocks for histone does modification is similar consequences. DNA is inaccessible to transcriptional factors. Chromatin is the state procedure which DNA is packaged within another cell. Epigenetics: Tools and technologies. Which fear of chemical modification would you expect go be associated with highly condensed chromatin? Unraveling a possible mechanism to heterochromatin is distinct higher order compartments, does histone modification affect euchromatin dynamics.
    [Show full text]