Histone Crosstalk Directed by H2B Ubiquitination Is Required for Chromatin Boundary Integrity
Genomic maps of chromatin modifications have provided evidence for the partitioning of genomes into domains of distinct chromatin states, which assist coordinated gene regulation. The maintenance of chromatin domain integrity can require the setting of boundaries. The HS4 insulator element marks the 3′ boundary of a heterochromatin region located upstream of the chicken β-globin gene cluster. Here we show that HS4 recruits the E3 ligase RNF20/BRE1A to mediate H2B mono-ubiquitination (H2Bub1) at this insulator. Knockdown experiments show that RNF20 is required for H2Bub1 and processive H3K4 methylation. Depletion of RNF20 results in a collapse of the active histone modification signature at the HS4 chromatin boundary, where H2Bub1, H3K4 methylation, and hyperacetylation of H3, H4, and H2A.Z are rapidly lost. A remarkably similar set of events occurs at the HSA/HSB regulatory elements of the FOLR1 gene, which mark the 5′ boundary of the same heterochromatin region. We find that persistent H2Bub1 at the HSA/HSB and HS4 elements is required for chromatin boundary integrity. The loss of boundary function leads to the sequential spreading of H3K9me2, H3K9me3, and H4K20me3 over the entire 50 kb FOLR1 and β-globin region and silencing of FOLR1 expression. These findings show that the HSA/HSB and HS4 boundary elements direct a cascade of active histone modifications that defend the FOLR1 and β-globin gene loci from the pervasive encroachment of an adjacent heterochromatin domain. We propose that many gene loci employ H2Bub1-dependent boundaries to prevent heterochromatin spreading.
Vyšlo v časopise:
Histone Crosstalk Directed by H2B Ubiquitination Is Required for Chromatin Boundary Integrity. PLoS Genet 7(7): e32767. doi:10.1371/journal.pgen.1002175
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002175
Souhrn
Genomic maps of chromatin modifications have provided evidence for the partitioning of genomes into domains of distinct chromatin states, which assist coordinated gene regulation. The maintenance of chromatin domain integrity can require the setting of boundaries. The HS4 insulator element marks the 3′ boundary of a heterochromatin region located upstream of the chicken β-globin gene cluster. Here we show that HS4 recruits the E3 ligase RNF20/BRE1A to mediate H2B mono-ubiquitination (H2Bub1) at this insulator. Knockdown experiments show that RNF20 is required for H2Bub1 and processive H3K4 methylation. Depletion of RNF20 results in a collapse of the active histone modification signature at the HS4 chromatin boundary, where H2Bub1, H3K4 methylation, and hyperacetylation of H3, H4, and H2A.Z are rapidly lost. A remarkably similar set of events occurs at the HSA/HSB regulatory elements of the FOLR1 gene, which mark the 5′ boundary of the same heterochromatin region. We find that persistent H2Bub1 at the HSA/HSB and HS4 elements is required for chromatin boundary integrity. The loss of boundary function leads to the sequential spreading of H3K9me2, H3K9me3, and H4K20me3 over the entire 50 kb FOLR1 and β-globin region and silencing of FOLR1 expression. These findings show that the HSA/HSB and HS4 boundary elements direct a cascade of active histone modifications that defend the FOLR1 and β-globin gene loci from the pervasive encroachment of an adjacent heterochromatin domain. We propose that many gene loci employ H2Bub1-dependent boundaries to prevent heterochromatin spreading.
Zdroje
1. DeSBabuMM 2010 Genomic neighbourhood and the regulation of gene expression. Curr Opin Cell Biol 22 326 333
2. de WitEvan SteenselB 2009 Chromatin domains in higher eukaryotes: insights from genome-wide mapping studies. Chromosoma 118 25 36
3. HawkinsRDHonGCLeeLKNgoQListerR 2010 Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6 479 491
4. Peric-HupkesDMeulemanWPagieLBruggemanSWSoloveiI 2010 Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell 38 603 613
5. FilionGJvan BemmelJGBraunschweigUTalhoutWKindJ 2010 Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143 212 224
6. KleinjanDALetticeLA 2008 Long-range gene control and genetic disease. Adv Genet 61 339 388
7. GiermanHJIndemansMHKosterJGoetzeSSeppenJ 2007 Domain-wide regulation of gene expression in the human genome. Genome Res 17 1286 1295
8. GrewalSIJiaS 2007 Heterochromatin revisited. Nat Rev Genet 8 35 46
9. GasznerMFelsenfeldG 2006 Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 7 703 713
10. ValenzuelaLKamakakaRT 2006 Chromatin insulators. Annu Rev Genet 40 107 138
11. WallaceJAFelsenfeldG 2007 We gather together: insulators and genome organization. Curr Opin Genet Dev 17 400 407
12. WestAGFraserP 2005 Remote control of gene transcription. Hum Mol Genet 14 Spec No 1 R101 111
13. LittMDSimpsonMGasznerMAllisCDFelsenfeldG 2001 Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus. Science 293 2453 2455
14. LittMDSimpsonMRecillas-TargaFPrioleauMNFelsenfeldG 2001 Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci. EMBO J 20 2224 2235
15. PrioleauMNNonyPSimpsonMFelsenfeldG 1999 An insulator element and condensed chromatin region separate the chicken beta-globin locus from an independently regulated erythroid-specific folate receptor gene. EMBO J 18 4035 4048
16. ChungJHWhiteleyMFelsenfeldG 1993 A 5′ element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74 505 514
17. PikaartMJRecillas-TargaFFelsenfeldG 1998 Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators. Genes Dev 12 2852 2862
18. Recillas-TargaFPikaartMJBurgess-BeusseBBellACLittMD 2002 Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities. Proc Natl Acad Sci U S A 99 6883 6888
19. BellACWestAGFelsenfeldG 1999 The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98 387 396
20. YaoSOsborneCSBharadwajRRPasceriPSukonnikT 2003 Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Res 31 5317 5323
21. DicksonJGowherHStrogantsevRGasznerMHairA 2010 VEZF1 elements mediate protection from DNA methylation. PLoS Genet 6 e1000804 doi:10.1371/journal.pgen.1000804
22. HuangSLiXYusufzaiTMQiuYFelsenfeldG 2007 USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier. Mol Cell Biol 27 7991 8002
23. HuangSLittMFelsenfeldG 2005 Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications. Genes Dev 19 1885 1893
24. WestAGHuangSGasznerMLittMDFelsenfeldG 2004 Recruitment of histone modifications by USF proteins at a vertebrate barrier element. Mol Cell 16 453 463
25. BruceKMyersFAMantouvalouELefevrePGreavesI 2005 The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken. Nucleic Acids Res 33 5633 5639
26. LeeJSSmithEShilatifardA 2010 The language of histone crosstalk. Cell 142 682 685
27. OsleyMA 2006 Regulation of histone H2A and H2B ubiquitylation. Brief Funct Genomic Proteomic 5 179 189
28. ShilatifardA 2006 Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75 243 269
29. KimJGuermahMMcGintyRKLeeJSTangZ 2009 RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 137 459 471
30. WeakeVMWorkmanJL 2008 Histone ubiquitination: triggering gene activity. Mol Cell 29 653 663
31. KouzaridesT 2007 Chromatin modifications and their function. Cell 128 693 705
32. TavernaSDLiHRuthenburgAJAllisCDPatelDJ 2007 How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14 1025 1040
33. VermeulenMEberlHCMatareseFMarksHDenissovS 2010 Quantitative Interaction Proteomics and Genome-wide Profiling of Epigenetic Histone Marks and Their Readers. Cell 142 967 980
34. JinCFelsenfeldG 2007 Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes Dev 21 1519 1529
35. GroudineMWeintraubH 1981 Activation of globin genes during chicken development. Cell 24 393 401
36. ZhuBZhengYPhamADMandalSSErdjument-BromageH 2005 Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell 20 601 611
37. KimJHakeSBRoederRG 2005 The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol Cell 20 759 770
38. Recillas-TargaFValadez-GrahamVFarrellCM 2004 Prospects and implications of using chromatin insulators in gene therapy and transgenesis. Bioessays 26 796 807
39. AmouyalM 2010 Gene insulation. Part I: natural strategies in yeast and Drosophila. Biochem Cell Biol 88 875 884
40. DhillonNRaabJGuzzoJSzyjkaSJGangadharanS 2009 DNA polymerase epsilon, acetylases and remodellers cooperate to form a specialized chromatin structure at a tRNA insulator. EMBO J 28 2583 2600
41. OkiMValenzuelaLChibaTItoTKamakakaRT 2004 Barrier proteins remodel and modify chromatin to restrict silenced domains. Mol Cell Biol 24 1956 1967
42. LinNLiXCuiKChepelevITieF 2011 A Barrier-only Boundary Element Delimits the Formation of Facultative Heterochromatin in Drosophila and Vertebrates. Mol Cell Biol
43. HwangWWVenkatasubrahmanyamSIanculescuAGTongABooneC 2003 A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol Cell 11 261 266
44. DionMFKaplanTKimMBuratowskiSFriedmanN 2007 Dynamics of replication-independent histone turnover in budding yeast. Science 315 1405 1408
45. OkiMKamakakaRT 2005 Barrier function at HMR. Mol Cell 19 707 716
46. ZhouBOWangSSXuLXMengFLXuanYJ 2010 SWR1 complex poises heterochromatin boundaries for antisilencing activity propagation. Mol Cell Biol 30 2391 2400
47. HenryKWBergerSL 2002 Trans-tail histone modifications: wedge or bridge? Nat Struct Biol 9 565 566
48. SunZWAllisCD 2002 Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418 104 108
49. ChandrasekharanMBHuangFSunZW 2009 Ubiquitination of histone H2B regulates chromatin dynamics by enhancing nucleosome stability. Proc Natl Acad Sci U S A 106 16686 16691
50. FlemingABKaoCFHillyerCPikaartMOsleyMA 2008 H2B ubiquitylation plays a role in nucleosome dynamics during transcription elongation. Mol Cell 31 57 66
51. TannyJCErdjument-BromageHTempstPAllisCD 2007 Ubiquitylation of histone H2B controls RNA polymerase II transcription elongation independently of histone H3 methylation. Genes Dev 21 835 847
52. ChandrasekharanMBHuangFChenYCSunZW 2010 Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination. Mol Cell Biol 30 3216 3232
53. NakanishiSSandersonBWDelventhalKMBradfordWDStaehling-HamptonK 2008 A comprehensive library of histone mutants identifies nucleosomal residues required for H3K4 methylation. Nat Struct Mol Biol 15 881 888
54. ShahbazianMDZhangKGrunsteinM 2005 Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Mol Cell 19 271 277
55. LeeJSShuklaASchneiderJSwansonSKWashburnMP 2007 Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS. Cell 131 1084 1096
56. WuMWangPFLeeJSMartin-BrownSFlorensL 2008 Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS. Mol Cell Biol 28 7337 7344
57. RuthenburgAJAllisCDWysockaJ 2007 Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell 25 15 30
58. LathamJADentSY 2007 Cross-regulation of histone modifications. Nat Struct Mol Biol 14 1017 1024
59. HungTBindaOChampagneKSKuoAJJohnsonK 2009 ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation. Mol Cell 33 248 256
60. WangZZangCCuiKSchonesDEBarskiA 2009 Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138 1019 1031
61. WysockaJSwigutTXiaoHMilneTAKwonSY 2006 A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442 86 90
62. MinskyNShemaEFieldYSchusterMSegalE 2008 Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells. Nat Cell Biol 10 483 488
63. SchulzeJMJacksonJNakanishiSGardnerJMHentrichT 2009 Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation. Mol Cell 35 626 641
64. ChungJHBellACFelsenfeldG 1997 Characterization of the chicken beta-globin insulator. Proc Natl Acad Sci U S A 94 575 580
65. GilesKEGhirlandoRFelsenfeldG 2010 Maintenance of a constitutive heterochromatin domain in vertebrates by a Dicer-dependent mechanism. Nat Cell Biol 12 94 99; sup pp 91–96
66. WeakeVMWorkmanJL 2010 Inducible gene expression: diverse regulatory mechanisms. Nat Rev Genet 11 426 437
67. Rodriguez-NavarroS 2009 Insights into SAGA function during gene expression. EMBO Rep 10 843 850
68. WoodASchneiderJDoverJJohnstonMShilatifardA 2005 The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS. Mol Cell 20 589 599
69. TalbertPBHenikoffS 2006 Spreading of silent chromatin: inaction at a distance. Nat Rev Genet 7 793 803
70. HinesKACrydermanDEFlanneryKMYangHVitaliniMW 2009 Domains of heterochromatin protein 1 required for Drosophila melanogaster heterochromatin spreading. Genetics 182 967 977
71. KwonSHWorkmanJL 2008 The heterochromatin protein 1 (HP1) family: put away a bias toward HP1. Mol Cells 26 217 227
72. SchottaGLachnerMSarmaKEbertASenguptaR 2004 A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev 18 1251 1262
73. HallIMShankaranarayanaGDNomaKAyoubNCohenA 2002 Establishment and maintenance of a heterochromatin domain. Science 297 2232 2237
74. SimsJKHoustonSIMagazinnikTRiceJC 2006 A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. J Biol Chem 281 12760 12766
75. ShinKJWallEAZavzavadjianJRSantatLALiuJ 2006 A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression. Proc Natl Acad Sci U S A 103 13759 13764
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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