The molecular hallmarks of epigenetic control

Nature Reviews Genetics, Год журнала: 2016, Номер 17(8), С. 487 - 500

Опубликована: Июнь 27, 2016

Язык: Английский

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Phase separation drives heterochromatin domain formation

Nature, Год журнала: 2017, Номер 547(7662), С. 241 - 245

Опубликована: Июнь 20, 2017

Язык: Английский

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DNA Methylation in Mammals

Cold Spring Harbor Perspectives in Biology, Год журнала: 2014, Номер 6(5), С. a019133 - a019133

Опубликована: Май 1, 2014

En Li1 and Yi Zhang2 1China Novartis Institutes for BioMedical Research, Pudong New Area, Shanghai 201203, China 2Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115 Correspondence: en.li{at}novartis.com

Язык: Английский

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The interplay of histone modifications – writers that read

EMBO Reports, Год журнала: 2015, Номер 16(11), С. 1467 - 1481

Опубликована: Окт. 16, 2015

Review16 October 2015Open Access The interplay of histone modifications – writers that read Tianyi Zhang Developmental Epigenetics, Department Biochemistry, University Oxford, UK Search for more papers by this author Sarah Cooper Corresponding Author Neil Brockdorff Information Zhang1,‡, 1,‡ and Brockdorff1 1Developmental ‡These authors contributed equally to work *Corresponding author. Tel: +44 1865 613230; E-mail: [email protected] EMBO Reports (2015)16:1467-1481https://doi.org/10.15252/embr.201540945 See the Glossary abbreviations used in article. PDFDownload PDF article text main figures. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Histones are subject a vast array posttranslational including acetylation, methylation, phosphorylation, ubiquitylation. these play important roles normal development their mutation or misregulation is linked with both genetic disorders various cancers. Readers marks contain protein domains allow recruitment chromatin. Interestingly, often which can chromatin marks, allowing reinforcement through positive feedback loop inhibition activity other modifications. We discuss how such result states robust be epigenetically maintained cell division. describe implications regulatory systems relation H3K4me3, H3K79me3, H3K36me3 associated active genes H3K27me3 H3K9me3 have been transcriptional repression. also review crosstalk between repressive modifications, illustrated Polycomb Trithorax histone-modifying proteins, may defining gene expression during development. AEPB2 AE-binding 2 ASH2L absent, small, homeotic-like ATRX5/6 Arabidopsis Trithorax-related 5/6 BEND3 Ben domain containing 3 BLOCS broad local enrichments BRE1 Brefeldin-A sensitivity 1 CBX chromobox CDYL chromodomain protein, Y-like CFP1 CXXC finger ChIP-sequencing immunoprecipitation followed DNA sequencing CpG cytosine-phosphate-guanine CTCF CCCTC-binding factor CTBP2 C-terminal-binding CTD C-terminal DNMT3A/B methyltransferase 3A/B DOT1 disruptor telomeric silencing DOT1L DOT1-like DPY30 dumpy-30 homolog EAF3 Esa1p-associated EED embryonic ectoderm ESC stem EZH2/1 enhancer zeste 2/1 FRAP fluorescence recovery after photobleaching G9a/GLP G9a G9a-like H2AK119u1 H2A lysine 119 monoubiqutination H2BK120u1 H2B 120 H2BK34u1 34 H3K27me1/2/3 H3 27 mono/di/trimethylation H3K36me1/2/3 36 H3K4me1/2/3 4 H3K9me1/2/3 9 HAT acetyltransferase HBO1 bound ORC HDAC deactylase complex HMT Hox homeobox-containing HP1 heterochromatin JARID2 jumonji, AT-rich interactive KDM2A/B demethylase 2A/B MBD methyl binding MES-4 mesoderm expressed MLL1/2/3/4 mixed-lineage leukemia 1/2/3/4 MSL1/2 male-specific lethal 1/2 NO66 nucleolar 66 NSD1/2/3 nuclear receptor-binding SET 1/2/3 NuA3/4 nucleosomal H3/H4 NURD nucleosome remodeling deacetylase P300/CBP P300- CREB-binding PAF polymerase-associated PCGF1/2/3/4/5/6 group ring 1/2/3/4/5/6 PCL1/2/3 Polycomb-like PH polyhomeotic PHD plant homeodomain Pol II RNA polymerase PRC1 PRC2 RAD6 ras-related diabetes 6 RBBP5 retinoblastoma-binding 5 RING1A/B really interesting new 1A/B RNF20/40 20/40 RpAb46/48 Rb-associated 46/48 RPD3S reduced potassium dependency 3S RYBP RING1- YY1-binding SAGA Spt-Ada-Gcn5 Su(var)3-9, enhancer-of-zeste SETD1A/B SETD2 SETMAR mariner transposase fusion SMYD2 MYND domain-containing SUV3-9 H1/H2 suppressor variegation 3-9 SUZ12 Suppressor 12 TrxG TSS transcription start site WDR5 WD repeat-containing YAF2 YY1-associated ZMYND11 zinc finger, MYND-type 11 Introduction In eukaryotes, packaged form basic unit chromatin, nucleosome, comprised 147 bp wrapped around octamer made two dimers tetramer H4 proteins. N- tails protrude from core potential interact adjacent nucleosomes linker DNA. All histones posttranslationally modified, sites modification on tails. These regulate structure directly frequently act as non-histone proteins most abundant ubiquitylation, although many reported (reviewed recently 1). Transcriptionally silent characterized distinct combinations thereof. Active typically carry high levels acetylation tails, trimethylation 4, 79, ubiquitylation H2B, (Fig Marks repressed include 27, 119, chromatin-modifying enzymes catalyze recruited target sequence-specific DNA-binding factors particular genes. However, general features its global CG content methylation status Zn-finger CxxC present 2. Equally, direct associate machinery, leading accumulation specific H3K4me3 H3K36me3. Figure 1. distribution over Download figure PowerPoint Given large number different combinatorial complexity vast. Advances technology past decade allowed us map co-localization at high-resolution genome wide, while mass spectrometry, combination stable isotope labeling, enables analysis dynamics level single tail. spectrometric data suggest there either likely occur together, mutually exclusive, suggesting marks. Such cis same tail, trans neighboring within domain. patterns established dynamic readers, writers, erasers. Importantly, place chromatin-reading bind preexisting Studies shown positively negatively catalytic resulting negative loops. Therefore, required establishment maintenance memory switching states. review, we will focus several examples mechanisms formation, reinforcement, 2). states, principles seen applicable plethora whose function still unclear. Crosstalk genesChromatin reinforce each mechanisms. holds true Additionally, mutual opposite state eukaryotic organisms, regulated synergistic actions multiple factors, but not limited to, remodelers, presence variants H3K27ac H3K4me1 enhancers 3, found promoters 456. bodies enriched 7, H3K79me3 8, 910, increasing toward 3′ end 11. creating an open recruit effectors mediate transcriptionally competent state. While fully understood, evidence deposition proper regulation expression. Positive role Establishment highly conserved association evolutionarily eukaryotes. mammals, H3K4 catalyzed six related homologs yeast SET1—SETD1A, SETD1B, MLL1, MLL2, MLL3, MLL4 12. complexes SETD1/MLL subunits four WDR5, RBBP5, ASH2L, DPY30, well complex-specific 131415. hallmark distributed along promoter regions 61617. Work shows SET1 associates Ser5-phosphorylated initiating co-transcriptionally deposited 18 3). SETD1 MLL mediated type-specific coactivators 1920212223. However higher organisms especially, play. 3. H2BK120u1The II, co-transcriptionally. (associated SETD1) MLL1/2 de novo via islands. possibly recognition subunit. Notably, coupled islands, CpG- GC-dense predominately unmethylated 50–70% vertebrate 24. A biochemical link CpGI was eluciated discovery specifically binds nonmethylated CpGs subunit marked correlated 2526. Emerging suggests vivo, MLL2 responsible maintaining low 2728, SETD1-specific preferentially 29. ESCs, developmentally bivalent harbor mark 30. it has suggested ability sample CpGIs wide poise rapid activation upon differentiation. own mark, H3K4me3. known mediates interaction 313233. third MLL1 locus 34. Other remain further 35. involved once established, deposition. H2BK120u1, One best-studied pathways stimulation (or H2BK123u1 yeast). yeast, ubiquitin ligase RAD6/BRE1 initiation localizes 36. Depletion H2BK123 causes severe loss 3738. This does extend H3K36me3, another lies close proximity H3K79 exposed surface, influenced deletion residues tail 39. humans, situation complex, solely dependent H2BK120u1. Human peaks moreover Ser5- Ser2-phosphorylated forms 40. As such, marker genes, yet exact remains discovered. knockdown leads reduction 41 More recently, studies MSL1/MSL2 E3 catalyzes revealed 42. Both now allosterically stimulate 43. Sites H2BK120 H2BK34 reside surface provide favorable substrate all one mechanism whereby results H2Bub, subsequently activates methyltransferases. Histone cellular processes transcription. Acetylation unique structural motif, bromodomain, recognizes acetylated lysines 44. Besides effectors, proposed physically alter neutralizing charge disrupting intra- internucleosomal interactions, lead environment permissible Lysine three globular H3K56, H3K64, H3K122, lie H3–DNA interface, disrupt electrostatic interactions 454647. H3K122ac promote vitro stimulating eviction 47. acetylations enhance unwrapping, sensitizes salt-induced dissociation 48. coexist promotes downstream HATs 4). readers identified complexes. SGF29, component contains tandem tudor overlaps promoters. SGF29 H3K9ac 49. Similarly, NuA3 50 NuA4 51, mammalian 52 fingers Dynamic turnover action p300/CBP 53. H3K4me3-linked eukaryotes fly, mouse, human. Loss CpGI-associated ESCs Further using Dictyostelium discoideum model knockout lost 54. rather than itself key 55). support this, members H3K4me3-binding HDACs 56. promoter-associated before initiation, H3K4me3-dependent co-targeting HATS facilitate acetylation. above illustrate pathway cooperativity hyperacetylation ensuring regulation. 4. Interplay acetylationH3K4me3 reinforces Various H3K36 H3K36me1/2 elongating H3K36me2/3 recruits deacetylate bodies. deacetylation Methylation mono-, di-, exist SET2. Mammals hand family, ASH1L, SMYD2, SETMAR, SETD2, sole enzyme vivo 57) uncoupling evolution alludes biologically transcribed increase Set2 predominant ends 585960. Like bromodomain-containing deacetylates prevents spurious 616263. TSS, H3K36me2/3-mediated wake machinery prevent aberrant body. exclusivity integrity. idea supported showing lack H3K36me2 demethylases co-localize promoters, removal 6465. recognized PWWP domain, chromatin-binding 66676869. NSD family methyltransferases 70 peptides 69. implies propagation H3K36me1 certain sites. Mono-/dimethylation pervasive restricted euchromatin 7172. biological mono-/dimethylation unknown, though mutations NSD2 upregulation profiles cancers 737475. right serve subsequent SETD2-mediated trimethylation. spreading 7677, discussed below. Repressive ubiquitinylation hallmarks loci. formation facultative heterochromatin, whereas H3K9me2/3, having constitutive plays part regulating Complex (PRC2) subunits, EZH2/1, SUZ12, EED, RBAP46/8 78. EZH2 EZH1), only functional context full 798081. There accessory types PRC2: PRC2.1 includes (PCL1/2/3) PRC2.2 AEBP2 82. unclear, they modulate targeting able trimethylate H3K27, some dispute if H3K27me1 methyltransferase. very roles, repression, recent 83. H3K27me2 prevalent genome, MS/MS demonstrating accounts 60–80% mESCs 84, little about well-characterized terms critical repression regulators silencing, H3K27. ES cells, thousand clusters, where heritable 85. inactive X chromosome 86. differentiated types, larger H3K27me3, termed BLOCS, visualized loci 87. described above, expression, loops domains. aromatic cage 88. It deposits domains, could inheritance division 89. stimulated dense (A31-R42) 90. way, (PRC1) modify monoubiquitylation 119. subunit, PCGF 91. thought define class example, PCGF2 (MEL18) PCGF4 (BMI) make up canonical (2,4,6,7,8) 92. Variant exclusive 9193. variant complexes, RING1B/PCGF1/RYBP/BCOR/KDM2B, implicated compared 9194. ubiquitin-binding 95. establish maintain similar manner H3K27me3. PRC2, 96979899. hierarchical model, placed PRC1, explain co-recruitment 100. occurs 101. Hence, targets would become established. account since even absence RYBP-containing localize correct 93102. laboratories

Язык: Английский

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Ten principles of heterochromatin formation and function

Nature Reviews Molecular Cell Biology, Год журнала: 2017, Номер 19(4), С. 229 - 244

Опубликована: Дек. 13, 2017

Язык: Английский

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H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes

Trends in Genetics, Год журнала: 2015, Номер 32(1), С. 29 - 41

Опубликована: Дек. 12, 2015

Язык: Английский

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Comparative analysis of metazoan chromatin organization

Nature, Год журнала: 2014, Номер 512(7515), С. 449 - 452

Опубликована: Авг. 26, 2014

A large collection of new modENCODE and ENCODE genome-wide chromatin data sets from cell lines developmental stages in worm, fly human are analysed; this reveals many conserved features organization among the three organisms, as well notable differences composition locations repressive chromatin. This study describes numerous Homo sapiens, Drosophila melanogaster Caenorhabditis elegans generated by consortia. The results point to while identifying Genome function is dynamically regulated part chromatin, which consists histones, non-histone proteins RNA molecules that package DNA. Studies have contributed substantially our understanding molecular mechanisms genome humans, revealed conservation components mechanisms1,2,3. Nevertheless, organisms markedly different sizes, chromosome architecture gene organization. On chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes dispersed heterochromatin-like regions enriched distal chromosomal 'arms', centromeres distributed along their lengths4,5. To systematically investigate associated regulation across species, we analysed a human. Here present over 800 consortia, bringing total 1,400. Comparison combinatorial patterns histone modifications, nuclear lamina-associated domains, large-scale topological environment at promoters enhancers, nucleosome positioning, DNA replication organisms. We also find These analyses provide rich resource comparative species-specific investigations composition, function.

Язык: Английский

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Epigenetic Regulation in Plants

Cold Spring Harbor Perspectives in Biology, Год журнала: 2014, Номер 6(12), С. a019315 - a019315

Опубликована: Дек. 1, 2014

Craig S. Pikaard1 and Ortrun Mittelsten Scheid2 1Department of Biology, Department Molecular Cellular Biochemistry, Howard Hughes Medical Institute, Indiana University, Bloomington, 47405 2Gregor Mendel-Institute Plant Austrian Academy Sciences, 1030 Vienna, Austria Correspondence: ortrun.mittelsten_scheid{at}gmi.oeaw.ac.at

Язык: Английский

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Histone lysine methyltransferases in biology and disease

Nature Structural & Molecular Biology, Год журнала: 2019, Номер 26(10), С. 880 - 889

Опубликована: Окт. 1, 2019

Язык: Английский

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Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(9), С. 623 - 640

Опубликована: Май 13, 2022

Язык: Английский

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