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High-Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells


H1 linker histones facilitate higher-order chromatin folding and are essential for mammalian development. To achieve high-resolution mapping of H1 variants H1d and H1c in embryonic stem cells (ESCs), we have established a knock-in system and shown that the N-terminally tagged H1 proteins are functionally interchangeable to their endogenous counterparts in vivo. H1d and H1c are depleted from GC- and gene-rich regions and active promoters, inversely correlated with H3K4me3, but positively correlated with H3K9me3 and associated with characteristic sequence features. Surprisingly, both H1d and H1c are significantly enriched at major satellites, which display increased nucleosome spacing compared with bulk chromatin. While also depleted at active promoters and enriched at major satellites, overexpressed H10 displays differential binding patterns in specific repetitive sequences compared with H1d and H1c. Depletion of H1c, H1d, and H1e causes pericentric chromocenter clustering and de-repression of major satellites. These results integrate the localization of an understudied type of chromatin proteins, namely the H1 variants, into the epigenome map of mouse ESCs, and we identify significant changes at pericentric heterochromatin upon depletion of this epigenetic mark.


Vyšlo v časopise: High-Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells. PLoS Genet 9(4): e32767. doi:10.1371/journal.pgen.1003417
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003417

Souhrn

H1 linker histones facilitate higher-order chromatin folding and are essential for mammalian development. To achieve high-resolution mapping of H1 variants H1d and H1c in embryonic stem cells (ESCs), we have established a knock-in system and shown that the N-terminally tagged H1 proteins are functionally interchangeable to their endogenous counterparts in vivo. H1d and H1c are depleted from GC- and gene-rich regions and active promoters, inversely correlated with H3K4me3, but positively correlated with H3K9me3 and associated with characteristic sequence features. Surprisingly, both H1d and H1c are significantly enriched at major satellites, which display increased nucleosome spacing compared with bulk chromatin. While also depleted at active promoters and enriched at major satellites, overexpressed H10 displays differential binding patterns in specific repetitive sequences compared with H1d and H1c. Depletion of H1c, H1d, and H1e causes pericentric chromocenter clustering and de-repression of major satellites. These results integrate the localization of an understudied type of chromatin proteins, namely the H1 variants, into the epigenome map of mouse ESCs, and we identify significant changes at pericentric heterochromatin upon depletion of this epigenetic mark.


Zdroje

1. Wolffe AP (1998) Chromatin: Structure and Function. San Diego, CA: Academic Press.

2. van Holde KE (1989) Chromatin: New York: Springer-Verlag.

3. BednarJ, HorowitzRA, GrigoryevSA, CarruthersLM, HansenJC, et al. (1998) Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proc Natl Acad Sci U S A 95: 14173–14178.

4. RobinsonPJ, FairallL, HuynhVA, RhodesD (2006) EM measurements define the dimensions of the “30-nm” chromatin fiber: evidence for a compact, interdigitated structure. Proc Natl Acad Sci U S A 103: 6506–6511.

5. RouthA, SandinS, RhodesD (2008) Nucleosome repeat length and linker histone stoichiometry determine chromatin fiber structure. Proc Natl Acad Sci U S A 105: 8872–8877.

6. HappelN, DoeneckeD (2009) Histone H1 and its isoforms: contribution to chromatin structure and function. Gene 431: 1–12.

7. FanY, NikitinaT, Morin-KensickiEM, ZhaoJ, MagnusonTR, et al. (2003) H1 linker histones are essential for mouse development and affect nucleosome spacing in vivo. Mol Cell Biol 23: 4559–4572.

8. LennoxRW, CohenLH (1983) The histone H1 complements of dividing and nondividing cells of the mouse. J Biol Chem 258: 262–268.

9. MedrzyckiM, ZhangY, McDonaldJF, FanY (2012) Profiling of linker histone variants in ovarian cancer. Front Biosci 17: 396–406.

10. WangZF, SirotkinAM, BucholdGM, SkoultchiAI, MarzluffWF (1997) The mouse histone H1 genes: gene organization and differential regulation. J Mol Biol 271: 124–138.

11. WarneboldtJ, HallerF, HorstmannO, DannerBC, FuzesiL, et al. (2008) Histone H1x is highly expressed in human neuroendocrine cells and tumours. BMC Cancer 8: 388.

12. SirotkinAM, EdelmannW, ChengG, Klein-SzantoA, KucherlapatiR, et al. (1995) Mice develop normally without the H1(0) linker histone. Proc Natl Acad Sci U S A 92: 6434–6438.

13. LinQ, SirotkinA, SkoultchiAI (2000) Normal spermatogenesis in mice lacking the testis-specific linker histone H1t. Mol Cell Biol 20: 2122–2128.

14. FanY, SirotkinA, RussellRG, AyalaJ, SkoultchiAI (2001) Individual somatic H1 subtypes are dispensable for mouse development even in mice lacking the H1(0) replacement subtype. Mol Cell Biol 21: 7933–7943.

15. RabiniS, FrankeK, SaftigP, BodeC, DoeneckeD, et al. (2000) Spermatogenesis in mice is not affected by histone H1.1 deficiency. Exp Cell Res 255: 114–124.

16. GunjanA, BrownDT (1999) Overproduction of histone H1 variants in vivo increases basal and induced activity of the mouse mammary tumor virus promoter. Nucleic Acids Res 27: 3355–3363.

17. AlamiR, FanY, PackS, TMS, BesseA, et al. (2003) Mammalian linker-histone subtypes differentially affect gene expression invivo. Proc Natl Acad Sci U S A 100: 5920–5925.

18. SanchoM, DianiE, BeatoM, JordanA (2008) Depletion of human histone H1 variants uncovers specific roles in gene expression and cell growth. PLoS Genet 4: e1000227 doi:10.1371/journal.pgen.1000227.

19. LuR, MarkowetzF, UnwinRD, LeekJT, AiroldiEM, et al. (2009) Systems-level dynamic analyses of fate change in murine embryonic stem cells. Nature 462: 358–362.

20. MeissnerA (2010) Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol 28: 1079–1088.

21. BernsteinBE, MikkelsenTS, XieX, KamalM, HuebertDJ, et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315–326.

22. CreyghtonMP, ChengAW, WelsteadGG, KooistraT, CareyBW, et al. (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 107: 21931–21936.

23. CreyghtonMP, MarkoulakiS, LevineSS, HannaJ, LodatoMA, et al. (2008) H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135: 649–661.

24. BirneyE, StamatoyannopoulosJA, DuttaA, GuigoR, GingerasTR, et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447: 799–816.

25. BernsteinBE, StamatoyannopoulosJA, CostelloJF, RenB, MilosavljevicA, et al. (2010) The NIH Roadmap Epigenomics Mapping Consortium. Nat Biotechnol 28: 1045–1048.

26. FanY, NikitinaT, ZhaoJ, FleuryTJ, BhattacharyyaR, et al. (2005) Histone h1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123: 1199–1212.

27. ZhangY, LiuZ, MedrzyckiM, CaoK, FanY (2012) Reduction of Hox gene expression by histone H1 depletion. PLoS ONE 7: e38829 doi:10.1371/journal.pone.0038829.

28. ClausellJ, HappelN, HaleTK, DoeneckeD, BeatoM (2009) Histone H1 subtypes differentially modulate chromatin condensation without preventing ATP-dependent remodeling by SWI/SNF or NURF. PLoS ONE 4: e0007243 doi: 10.1371/journal.pone.0007243.

29. Th'ngJP, SungR, YeM, HendzelMJ (2005) H1 family histones in the nucleus. Control of binding and localization by the C-terminal domain. J Biol Chem 280: 27809–27814.

30. MeergansT, AlbigW, DoeneckeD (1997) Varied expression patterns of human H1 histone genes in different cell lines. DNA Cell Biol 16: 1041–1049.

31. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.

32. KidderBL, YangJ, PalmerS (2008) Stat3 and c-Myc genome-wide promoter occupancy in embryonic stem cells. PLoS ONE 3: e3932 doi:10.1371/journal.pone.0003932.

33. LajugieJ, BouhassiraEE (2011) GenPlay, a multipurpose genome analyzer and browser. Bioinformatics 27: 1889–1893.

34. MikkelsenTS, KuM, JaffeDB, IssacB, LiebermanE, et al. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448: 553–560.

35. GuentherMG, LevineSS, BoyerLA, JaenischR, YoungRA (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130: 77–88.

36. ZangC, SchonesDE, ZengC, CuiK, ZhaoK, et al. (2009) A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25: 1952–1958.

37. ShinH, LiuT, ManraiAK, LiuXS (2009) CEAS: cis-regulatory element annotation system. Bioinformatics 25: 2605–2606.

38. BockC, HalachevK, BuchJ, LengauerT (2009) EpiGRAPH: user-friendly software for statistical analysis and prediction of (epi)genomic data. Genome Biol 10: R14.

39. JurkaJ (2000) Repbase update: a database and an electronic journal of repetitive elements. Trends Genet 16: 418–420.

40. JurkaJ, KapitonovVV, PavlicekA, KlonowskiP, KohanyO, et al. (2005) Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res 110: 462–467.

41. BockC, TomazouEM, BrinkmanAB, MullerF, SimmerF, et al. (2010) Quantitative comparison of genome-wide DNA methylation mapping technologies. Nat Biotechnol 28: 1106–1114.

42. BelancioVP, Roy-EngelAM, PochampallyRR, DeiningerP (2010) Somatic expression of LINE-1 elements in human tissues. Nucleic Acids Res 38: 3909–3922.

43. PackerAI, ManovaK, BachvarovaRF (1993) A discrete LINE-1 transcript in mouse blastocysts. Dev Biol 157: 281–283.

44. TreloganSA, MartinSL (1995) Tightly regulated, developmentally specific expression of the first open reading frame from LINE-1 during mouse embryogenesis. Proc Natl Acad Sci U S A 92: 1520–1524.

45. MartensJH, O'SullivanRJ, BraunschweigU, OpravilS, RadolfM, et al. (2005) The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J 24: 800–812.

46. WoodcockCL, SkoultchiAI, FanY (2006) Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14: 17–25.

47. ObergC, IzzoA, SchneiderR, WrangeO, BelikovS (2012) Linker histone subtypes differ in their effect on nucleosomal spacing in vivo. J Mol Biol 419: 183–197.

48. HsuTC, CooperJE, MaceMLJr, BrinkleyBR (1971) Arrangement of centromeres in mouse cells. Chromosoma 34: 73–87.

49. GuenatriM, BaillyD, MaisonC, AlmouzniG (2004) Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J Cell Biol 166: 493–505.

50. BreroA, EaswaranHP, NowakD, GrunewaldI, CremerT, et al. (2005) Methyl CpG-binding proteins induce large-scale chromatin reorganization during terminal differentiation. J Cell Biol 169: 733–743.

51. GilbertN, ThomsonI, BoyleS, AllanJ, RamsahoyeB, et al. (2007) DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction. J Cell Biol 177: 401–411.

52. PapaitR, PistoreC, GraziniU, BabbioF, CogliatiS, et al. (2008) The PHD domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin. Mol Biol Cell 19: 3554–3563.

53. ZhangY, CookeM, PanjwaniS, CaoK, KrauthB, et al. (2012) Histone h1 depletion impairs embryonic stem cell differentiation. PLoS Genet 8: e1002691 doi:10.1371/journal.pgen.1002691.

54. RudertF, BronnerS, GarnierJM, DolleP (1995) Transcripts from opposite strands of gamma satellite DNA are differentially expressed during mouse development. Mamm Genome 6: 76–83.

55. BerrettaJ, MorillonA (2009) Pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 10: 973–982.

56. Bouzinba-SegardH, GuaisA, FrancastelC (2006) Accumulation of small murine minor satellite transcripts leads to impaired centromeric architecture and function. Proc Natl Acad Sci U S A 103: 8709–8714.

57. ZlatanovaJ, DoeneckeD (1994) Histone H1 zero: a major player in cell differentiation? FASEB J 8: 1260–1268.

58. LiJY, PattersonM, MikkolaHK, LowryWE, KurdistaniSK (2012) Dynamic distribution of linker histone h1.5 in cellular differentiation. PLoS Genet 8: e1002879 doi:10.1371/journal.pgen.1002879.

59. KrishnakumarR, GambleMJ, FrizzellKM, BerrocalJG, KininisM, et al. (2008) Reciprocal binding of PARP-1 and histone H1 at promoters specifies transcriptional outcomes. Science 319: 819–821.

60. BraunschweigU, HoganGJ, PagieL, van SteenselB (2009) Histone H1 binding is inhibited by histone variant H3.3. EMBO J 28: 3635–3645.

61. IzaurraldeE, KasE, LaemmliUK (1989) Highly preferential nucleation of histone H1 assembly on scaffold-associated regions. J Mol Biol 210: 573–585.

62. MirkovitchJ, MiraultME, LaemmliUK (1984) Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold. Cell 39: 223–232.

63. KasE, IzaurraldeE, LaemmliUK (1989) Specific inhibition of DNA binding to nuclear scaffolds and histone H1 by distamycin. The role of oligo(dA).oligo(dT) tracts. J Mol Biol 210: 587–599.

64. BonnefoyE, BanduMT, DolyJ (1999) Specific binding of high-mobility-group I (HMGI) protein and histone H1 to the upstream AT-rich region of the murine beta interferon promoter: HMGI protein acts as a potential antirepressor of the promoter. Mol Cell Biol 19: 2803–2816.

65. TilloD, HughesTR (2009) G+C content dominates intrinsic nucleosome occupancy. BMC Bioinformatics 10: 442.

66. BannisterAJ, ZegermanP, PartridgeJF, MiskaEA, ThomasJO, et al. (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410: 120–124.

67. LachnerM, O'CarrollD, ReaS, MechtlerK, JenuweinT (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410: 116–120.

68. JonesDO, CowellIG, SinghPB (2000) Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays 22: 124–137.

69. NielsenAL, Oulad-AbdelghaniM, OrtizJA, RemboutsikaE, ChambonP, et al. (2001) Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol Cell 7: 729–739.

70. DaujatS, ZeisslerU, WaldmannT, HappelN, SchneiderR (2005) HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding. J Biol Chem 280: 38090–38095.

71. LuX, WontakalSN, EmelyanovAV, MorcilloP, KonevAY, et al. (2009) Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure. Genes Dev 23: 452–465.

72. GilbertN, AllanJ (2001) Distinctive higher-order chromatin structure at mammalian centromeres. Proc Natl Acad Sci U S A 98: 11949–11954.

73. ZhangXY, HorzW (1984) Nucleosomes are positioned on mouse satellite DNA in multiple highly specific frames that are correlated with a diverged subrepeat of nine base-pairs. J Mol Biol 176: 105–129.

74. LinxwellerW, HorzW (1985) Reconstitution experiments show that sequence-specific histone-DNA interactions are the basis for nucleosome phasing on mouse satellite DNA. Cell 42: 281–290.

75. PanettaG, ButtinelliM, FlausA, RichmondTJ, RhodesD (1998) Differential nucleosome positioning on Xenopus oocyte and somatic 5 S RNA genes determines both TFIIIA and H1 binding: a mechanism for selective H1 repression. J Mol Biol 282: 683–697.

76. Choo KHA (1997) The centromere. Oxford; New York: Oxford University Press. xiv, 304 p. p.

77. ProbstAV, AlmouzniG (2008) Pericentric heterochromatin: dynamic organization during early development in mammals. Differentiation 76: 15–23.

78. ThomasJO, ReesC, FinchJT (1992) Cooperative binding of the globular domains of histones H1 and H5 to DNA. Nucleic Acids Res 20: 187–194.

79. PetersAH, O'CarrollD, ScherthanH, MechtlerK, SauerS, et al. (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107: 323–337.

80. Harnicarova HorakovaA, GaliovaG, LegartovaS, KozubekS, MatulaP, et al. (2010) Chromocentre integrity and epigenetic marks. J Struct Biol 169: 124–133.

81. ProbstAV, OkamotoI, CasanovaM, El MarjouF, Le BacconP, et al. (2010) A strand-specific burst in transcription of pericentric satellites is required for chromocenter formation and early mouse development. Dev Cell 19: 625–638.

82. FanY, SkoultchiAI (2004) Genetic analysis of H1 linker histone subtypes and their functions in mice. Methods Enzymol 377: 85–107.

83. MedrzyckiM, ZhangY, CaoK, FanY (2012) Expression analysis of mammalian linker-histone subtypes. J Vis Exp 61: e3577 doi: 10.3791/3577.

84. BoyerLA, PlathK, ZeitlingerJ, BrambrinkT, MedeirosLA, et al. (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441: 349–353.

85. ZhouJ, SalequeS, ErmakovaO, SepulvedaMA, YangQ, et al. (2005) Changes in replication, nuclear location, and expression of the Igh locus after fusion of a pre-B cell line with a T cell line. J Immunol 175: 2317–2320.

86. BockC, ReitherS, MikeskaT, PaulsenM, WalterJ, et al. (2005) BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics 21: 4067–4068.

87. YamagataK, YamazakiT, MikiH, OgonukiN, InoueK, et al. (2007) Centromeric DNA hypomethylation as an epigenetic signature discriminates between germ and somatic cell lineages. Dev Biol 312: 419–426.

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