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Uncoupling Transcription from Covalent Histone Modification


The proper regulation of gene expression is of fundamental importance in the maintenance of normal growth and development. Misregulation of genes can lead to such outcomes as cancer, diabetes and neurodegenerative disease. A key step in gene regulation occurs during the transcription of the chromosomal DNA into messenger RNA by the enzyme, RNA polymerase II. Histones are small, positively charged proteins that package genomic DNA into arrays of bead-like particles termed nucleosomes, the principal components of chromatin. Increasing evidence suggests that nucleosomal histones play an active role in regulating transcription, and that this is derived in part from reversible chemical (“covalent”) modifications that take place on their amino acids. These histone modifications create novel surfaces on nucleosomes that can serve as docking sites for other proteins that control a gene's expression state. In this study we present evidence that contrary to the general case, covalent modifications typically associated with transcription are minimally used by genes embedded in a specialized, condensed chromatin structure termed heterochromatin in the model organism baker's yeast. Our observations are significant, for they suggest that gene transcription can occur in a living cell in the virtual absence of covalent modification of the chromatin template.


Vyšlo v časopise: Uncoupling Transcription from Covalent Histone Modification. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004202
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004202

Souhrn

The proper regulation of gene expression is of fundamental importance in the maintenance of normal growth and development. Misregulation of genes can lead to such outcomes as cancer, diabetes and neurodegenerative disease. A key step in gene regulation occurs during the transcription of the chromosomal DNA into messenger RNA by the enzyme, RNA polymerase II. Histones are small, positively charged proteins that package genomic DNA into arrays of bead-like particles termed nucleosomes, the principal components of chromatin. Increasing evidence suggests that nucleosomal histones play an active role in regulating transcription, and that this is derived in part from reversible chemical (“covalent”) modifications that take place on their amino acids. These histone modifications create novel surfaces on nucleosomes that can serve as docking sites for other proteins that control a gene's expression state. In this study we present evidence that contrary to the general case, covalent modifications typically associated with transcription are minimally used by genes embedded in a specialized, condensed chromatin structure termed heterochromatin in the model organism baker's yeast. Our observations are significant, for they suggest that gene transcription can occur in a living cell in the virtual absence of covalent modification of the chromatin template.


Zdroje

1. ElginSCR (1988) The formation and function of DNase hypersensitive sites in the process of gene activation. J Biol Chem 263: 19259–19262.

2. GrossDS, GarrardWT (1988) Nuclease hypersensitive sites in chromatin. Annu Rev Biochem 57: 159–197.

3. WeinerA, HughesA, YassourM, RandoOJ, FriedmanN (2010) High-resolution nucleosome mapping reveals transcription-dependent promoter packaging. Genome Res 20: 90–100.

4. XiY, YaoJ, ChenR, LiW, HeX (2011) Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation. Genome Res 21: 718–724.

5. LeeDY, HayesJJ, PrussD, WolffeAP (1993) A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72: 73–84.

6. LugerK, MaderAW, RichmondRK, SargentDF, RichmondTJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389: 251–260.

7. Shogren-KnaakM, IshiiH, SunJM, PazinMJ, DavieJR, et al. (2006) Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311: 844–847.

8. GovindCK, QiuH, GinsburgDS, RuanC, HofmeyerK, et al. (2010) Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes. Mol Cell 39: 234–246.

9. JenuweinT, AllisCD (2001) Translating the histone code. Science 293: 1074–1080.

10. StrahlBD, AllisCD (2000) The language of covalent histone modifications. Nature 403: 41–45.

11. LoWS, DugganL, EmreNC, BelotserkovskyaR, LaneWS, et al. (2001) Snf1–a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription. Science 293: 1142–1146.

12. BungardD, FuerthBJ, ZengPY, FaubertB, MaasNL, et al. (2010) Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation. Science 329: 1201–1205.

13. RuthenburgAJ, LiH, MilneTA, DewellS, McGintyRK, et al. (2011) Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell 145: 692–706.

14. KouzaridesT (2007) Chromatin modifications and their function. Cell 128: 693–705.

15. SmithE, ShilatifardA (2010) The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes. Mol Cell 40: 689–701.

16. PtashneM (2013) Epigenetics: core misconcept. Proc Natl Acad Sci U S A 110: 7101–7103.

17. HenikoffS, ShilatifardA (2011) Histone modification: cause or cog? Trends Genet 27: 389–396.

18. TrojerP, ReinbergD (2007) Facultative heterochromatin: is there a distinctive molecular signature? Mol Cell 28: 1–13.

19. ZhaoJ, SunBK, ErwinJA, SongJJ, LeeJT (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322: 750–756.

20. SimonJA, KingstonRE (2013) Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol Cell 49: 808–824.

21. PirrottaV, GrossDS (2005) Epigenetic silencing mechanisms in budding yeast and fruit fly: different paths, same destinations. Mol Cell 18: 395–398.

22. RuscheLN, KirchmaierAL, RineJ (2003) The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Ann Rev Biochem 72: 481–516.

23. OppikoferM, KuengS, GasserSM (2013) SIR-nucleosome interactions: Structure-function relationships in yeast silent chromatin. Gene 527: 10–25.

24. SekingerEA, GrossDS (2001) Silenced chromatin is permissive to activator binding and PIC recruitment. Cell 105: 403–414.

25. HoppeGJ, TannyJC, RudnerAD, GerberSA, DanaieS, et al. (2002) Steps in assembly of silent chromatin in yeast: Sir3-independent binding of a Sir2/Sir4 complex to silencers and role for Sir2-dependent deacetylation. Mol Cell Biol 22: 4167–4180.

26. RuscheLN, KirchmaierAL, RineJ (2002) Ordered nucleation and spreading of silenced chromatin in Saccharomyces cerevisiae. Mol Biol Cell 13: 2207–2222.

27. XuF, ZhangQ, ZhangK, XieW, GrunsteinM (2007) Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast. Mol Cell 27: 890–900.

28. MoazedD (2001) Common themes in the mechanisms of gene silencing. Mol Cell 8: 489–498.

29. YasuharaJC, WakimotoBT (2006) Oxymoron no more: the expanding world of heterochromatic genes. Trends Genet 22: 330–338.

30. LeeJT (2010) The X as model for RNA's niche in epigenomic regulation. Cold Spring Harb Perspect Biol 2: a003749.

31. HornD (2009) Antigenic variation: extending the reach of telomeric silencing. Curr Biol 19: R496–498.

32. LeeS, GrossDS (1993) Conditional silencing: The HMRE mating-type silencer exerts a rapidly reversible position effect on the yeast HSP82 heat shock gene. Mol Cell Biol 13: 727–738.

33. SekingerEA, GrossDS (1999) SIR repression of a yeast heat shock gene: UAS and TATA footprints persist within heterochromatin. EMBO J 18: 7041–7055.

34. LooS, RineJ (1994) Silencers and domains of generalized repression. Science 264: 1768–1771.

35. DonzeD, AdamsCR, RineJ, KamakakaRT (1999) The boundaries of the silenced HMR domain of Saccharomyces cerevisiae. Genes Dev 13: 698–708.

36. BiX, BroachJR (1999) UASrpg can function as heterochromatin boundary element in yeast. Genes Dev 13: 1089–1101.

37. KitadaT, KuryanBG, TranNN, SongC, XueY, et al. (2012) Mechanism for epigenetic variegation of gene expression at yeast telomeric heterochromatin. Genes Dev 26: 2443–2455.

38. ZhaoJ, Herrera-DiazJ, GrossDS (2005) Domain-wide displacement of histones by activated heat shock factor occurs independently of Swi/Snf and is not correlated with RNA polymerase II density. Mol Cell Biol 25: 8985–8999.

39. KremerSB, KimS, JeongJO, MoustafaYM, ChenA, et al. (2012) Role of Mediator in regulating Pol II elongation and nucleosome displacement in Saccharomyces cerevisiae. Genetics 191: 95–106.

40. KimS, GrossDS (2013) Mediator recruitment to heat shock genes requires dual Hsf1 activation domains and Mediator Tail subunits Med15 and Med16. J Biol Chem 288: 12197–12213.

41. SteinmetzEJ, WarrenCL, KuehnerJN, PanbehiB, AnsariAZ, et al. (2006) Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase. Mol Cell 24: 735–746.

42. GaoL, GrossDS (2008) Sir2 silences gene transcription by targeting the transition between RNA polymerase II initiation and elongation. Mol Cell Biol 28: 3979–3994.

43. VarvS, KristjuhanK, PeilK, LookeM, MahlakoivT, et al. (2010) Acetylation of H3 K56 is required for RNA polymerase II transcript elongation through heterochromatin in yeast. Mol Cell Biol 30: 1467–1477.

44. JohnsonA, WuR, PeetzM, GygiSP, MoazedD (2013) Heterochromatic gene silencing by activator interference and a transcription elongation barrier. J Biol Chem 288: 28771–28782.

45. KremerSB, GrossDS (2009) SAGA and Rpd3 chromatin modification complexes dynamically regulate heat shock gene structure and expression. J Biol Chem 284: 32914–32931.

46. VidaliG, BoffaLC, BradburyEM, AllfreyVG (1978) Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences. Proc Natl Acad Sci U S A 75: 2239–2243.

47. LiB, CareyM, WorkmanJL (2007) The role of chromatin during transcription. Cell 128: 707–719.

48. ZhouBO, WangSS, ZhangY, FuXH, DangW, et al. (2011) Histone H4 lysine 12 acetylation regulates telomeric heterochromatin plasticity in Saccharomyces cerevisiae. PLoS Genet 7: e1001272.

49. XuF, ZhangK, GrunsteinM (2005) Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121: 375–385.

50. VenkateshS, SmolleM, LiH, GogolMM, SaintM, et al. (2012) Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes. Nature 489: 452–455.

51. WilliamsSK, TruongD, TylerJK (2008) Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation. Proc Natl Acad Sci U S A 105: 9000–9005.

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

53. ShilatifardA (2008) Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 20: 341–348.

54. ShahbazianMD, ZhangK, GrunsteinM (2005) Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Mol Cell 19: 271–277.

55. GuertinMJ, MartinsAL, SiepelA, LisJT (2012) Accurate prediction of inducible transcription factor binding intensities in vivo. PLoS Genet 8: e1002610.

56. ZhangH, RobertsDN, CairnsBR (2005) Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123: 219–231.

57. RaisnerRM, HartleyPD, MeneghiniMD, BaoMZ, LiuCL, et al. (2005) Histone variant H2A.Z marks the 5′ ends of both active and inactive genes in euchromatin. Cell 123: 233–248.

58. GrantPA, EberharterA, JohnS, CookRG, TurnerBM, et al. (1999) Expanded lysine acetylation specificity of Gcn5 in native complexes. J Biol Chem 274: 5895–5900.

59. JinQ, YuLR, WangL, ZhangZ, KasperLH, et al. (2010) Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J 30: 249–262.

60. ErkinaTY, ErkineAM (2006) Displacement of histones at promoters of Saccharomyces cerevisiae heat shock genes is differentially associated with histone H3 acetylation. Mol Cell Biol 26: 7587–7600.

61. Strahl-BolsingerS, HechtA, LuoK, GrunsteinM (1997) SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev 11: 83–93.

62. Vega-PalasMA, Martin-FigueroaE, FlorencioFJ (2000) Telomeric silencing of a natural subtelomeric gene. Mol Gen Genet 263: 287–291.

63. ShahiP, GulshanK, NaarAM, Moye-RowleyWS (2010) Differential roles of transcriptional mediator subunits in regulation of multidrug resistance gene expression in Saccharomyces cerevisiae. Mol Biol Cell 21: 2469–2482.

64. TeboJ, DerS, FrevelM, KhabarKS, WilliamsBR, et al. (2003) Heterogeneity in control of mRNA stability by AU-rich elements. J Biol Chem 278: 12085–12093.

65. JiangC, PughBF (2009) A compiled and systematic reference map of nucleosome positions across the Saccharomyces cerevisiae genome. Genome Biol 10: R109.

66. TavernaSD, LiH, RuthenburgAJ, AllisCD, PatelDJ (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14: 1025–1040.

67. GrossDS, AdamsCC, LeeS, StentzB (1993) A critical role for heat shock transcription factor in establishing a nucleosome-free region over the TATA-initiation site of the yeast HSP82 heat shock gene. EMBO J 12: 3931–3945.

68. ErkineAM, MagroganSF, SekingerEA, GrossDS (1999) Cooperative binding of heat shock factor to the yeast HSP82 promoter in vivo and in vitro. Mol Cell Biol 19: 1627–1639.

69. PtashneM, GannA (1997) Transcriptional activation by recruitment. Nature 386: 569–577.

70. LenstraTL, BenschopJJ, KimT, SchulzeJM, BrabersNA, et al. (2011) The specificity and topology of chromatin interaction pathways in yeast. Mol Cell 42: 536–549.

71. HodlM, BaslerK (2012) Transcription in the absence of histone H3.2 and H3K4 methylation. Curr Biol 22: 2253–2257.

72. Tittel-ElmerM, BucherE, BrogerL, MathieuO, PaszkowskiJ, et al. (2010) Stress-induced activation of heterochromatic transcription. PLoS Genet 6: e1001175.

73. Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, et al.. (1995) Current Protocols in Molecular Biology: John Wiley & Sons, Inc.

74. FarrellyFW, FinkelsteinDB (1984) Complete sequence of heat shock-inducible HSP90 gene of Saccharomyces cerevisiae. J Biol Chem 259: 5745–5751.

75. MegeePC, MorganBA, MittmanBA, SmithMM (1990) Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. Science 247: 841–845.

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