Methylation of Histone H3 on Lysine 79 Associates with a Group of Replication Origins and Helps Limit DNA Replication Once per Cell Cycle

English version České info

Mammalian DNA replication starts at distinct chromosomal sites in a tissue-specific pattern coordinated with transcription, but previous studies have not yet identified a chromatin modification that correlates with the initiation of DNA replication at particular genomic locations. Here we report that a distinct fraction of replication initiation sites in the human genome are associated with a high frequency of dimethylation of histone H3 lysine K79 (H3K79Me2). H3K79Me2-containing chromatin exhibited the highest genome-wide enrichment for replication initiation events observed for any chromatin modification examined thus far (23.39% of H3K79Me2 peaks were detected in regions adjacent to replication initiation events). The association of H3K79Me2 with replication initiation sites was independent and not synergistic with other chromatin modifications. H3K79 dimethylation exhibited wider distribution on chromatin during S-phase, but only regions with H3K79 methylation in G1 and G2 were enriched in replication initiation events. H3K79 was dimethylated in a region containing a functional replicator (a DNA sequence capable of initiating DNA replication), but the methylation was not evident in a mutant replicator that could not initiate replication. Depletion of DOT1L, the sole enzyme responsible for H3K79 methylation, triggered limited genomic over-replication although most cells could continue to proliferate and replicate DNA in the absence of methylated H3K79. Thus, prevention of H3K79 methylation might affect regulatory processes that modulate the order and timing of DNA replication. These data are consistent with the hypothesis that dimethylated H3K79 associates with some replication origins and marks replicated chromatin during S-phase to prevent re-replication and preserve genomic stability.

Vyšlo v časopise: Methylation of Histone H3 on Lysine 79 Associates with a Group of Replication Origins and Helps Limit DNA Replication Once per Cell Cycle. PLoS Genet 9(6): e32767. doi:10.1371/journal.pgen.1003542
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003542

Souhrn

Zdroje

1. GomezM, BrockdorffN (2004) Heterochromatin on the inactive X chromosome delays replication timing without affecting origin usage. Proc Natl Acad Sci U S A 101: 6923–6928.

2. AntequeraF (2004) Genomic specification and epigenetic regulation of eukaryotic DNA replication origins. EMBO J 23: 4365–4370.

3. MartinMM, RyanM, KimR, ZakasAL, FuH, et al. (2011) Genome-wide depletion of replication initiation events in highly transcribed regions. Genome Res 21: 1822–32.

4. BesnardE, BabledA, LapassetL, MilhavetO, ParrinelloH, et al. (2012) Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs. Nat Struct Mol Biol 19: 837–844.

5. CayrouC, CoulombeP, VigneronA, StanojcicS, GanierO, et al. (2011) Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features. Genome Res 21: 1438–1449.

6. AladjemMI (2007) Replication in context: dynamic regulation of DNA replication patterns in metazoans. Nat Rev Genet 8: 588–600.

7. MechaliM (2010) Eukaryotic DNA replication origins: many choices for appropriate answers. Nat Rev Mol Cell Biol 11: 728–738.

8. AladjemMI, GroudineM, BrodyLL, DiekenES, FournierRE, et al. (1995) Participation of the human beta-globin locus control region in initiation of DNA replication. Science 270: 815–819.

9. KalejtaRF, LiX, MesnerLD, DijkwelPA, LinHB, et al. (1998) Distal sequences, but not ori-beta/OBR-1, are essential for initiation of DNA replication in the Chinese hamster DHFR origin. Molecular Cell 2: 797–806.

10. HayashidaT, OdaM, OhsawaK, YamaguchiA, HosozawaT, et al. (2006) Replication initiation from a novel origin identified in the Th2 cytokine cluster locus requires a distant conserved noncoding sequence. J Immunol 176: 5446–5454.

11. FengYQ, DespratR, FuH, OlivierE, LinCM, et al. (2006) DNA methylation supports intrinsic epigenetic memory in mammalian cells. PLoS Genet 2: e65.

12. HuangL, FuH, LinCM, ConnerAL, ZhangY, et al. (2011) Prevention of transcriptional silencing by a replicator-binding complex consisting of SWI/SNF, MeCP1, and hnRNP C1/C2. Mol Cell Biol 31: 3472–3484.

13. RybaT, HirataniI, LuJ, ItohM, KulikM, et al. (2010) Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types. Genome Res 20: 761–770.

14. GilbertDM (2012) Replication origins run (ultra) deep. Nat Struct Mol Biol 19: 740–742.

15. LacosteN, UtleyRT, HunterJM, PoirierGG, CoteJ (2002) Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem 277: 30421–30424.

16. FrederiksF, TzourosM, OudgenoegG, van WelsemT, FornerodM, et al. (2008) Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states. Nat Struct Mol Biol 15: 550–557.

17. SchulzeJM, JacksonJ, NakanishiS, GardnerJM, HentrichT, et al. (2009) Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation. Mol Cell 35: 626–641.

18. ZhouH, MaddenBJ, MuddimanDC, ZhangZ (2006) Chromatin assembly factor 1 interacts with histone H3 methylated at lysine 79 in the processes of epigenetic silencing and DNA repair. Biochemistry 45: 2852–2861.

19. ImH, ParkC, FengQ, JohnsonKD, KiekhaeferCM, et al. (2003) Dynamic regulation of histone H3 methylated at lysine 79 within a tissue-specific chromatin domain. J Biol Chem 278: 18346–18352.

20. MohanM, HerzHM, TakahashiYH, LinC, LaiKC, et al. (2010) Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev 24: 574–589.

21. JonesB, SuH, BhatA, LeiH, BajkoJ, et al. (2008) The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet 4: e1000190.

22. OnderTT, KaraN, CherryA, SinhaAU, ZhuN, et al. (2012) Chromatin-modifying enzymes as modulators of reprogramming. Nature 483: 598–602.

23. GiannattasioM, LazzaroF, PlevaniP, Muzi-FalconiM (2005) The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem 280: 9879–9886.

24. HuyenY, ZgheibO, DitullioRAJr, GorgoulisVG, ZacharatosP, et al. (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432: 406–411.

25. TatumD, LiS (2011) Evidence that the histone methyltransferase Dot1 mediates global genomic repair by methylating histone H3 on lysine 79. J Biol Chem 286: 17530–17535.

26. JacintoFV, BallestarE, EstellerM (2009) Impaired recruitment of the histone methyltransferase DOT1L contributes to the incomplete reactivation of tumor suppressor genes upon DNA demethylation. Oncogene 28: 4212–4224.

27. BerntKM, ZhuN, SinhaAU, VempatiS, FaberJ, et al. (2011) MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L. Cancer Cell 20: 66–78.

28. ChangMJ, WuH, AchilleNJ, ReisenauerMR, ChouCW, et al. (2011) Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res 70: 10234–10242.

29. WangP, LinC, SmithER, GuoH, SandersonBW, et al. (2009) Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Mol Cell Biol 29: 6074–6085.

30. OkadaY, FengQ, LinY, JiangQ, LiY, et al. (2005) hDOT1L links histone methylation to leukemogenesis. Cell 121: 167–178.

31. AladjemMI, RodewaldLW, KolmanJL, WahlGM (1998) Genetic dissection of a mammalian replicator in the human beta-globin locus. Science 281: 1005–1009.

32. KitsbergD, SeligS, KeshetI, CedarH (1993) Replication structure of the human beta-globin gene domain. Nature 366: 588–590.

33. WangL, LinCM, BrooksS, CimboraD, GroudineM, et al. (2004) The human beta-globin replication initiation region consists of two modular independent replicators. Mol Cell Biol 24: 3373–3386.

34. WangL, LinCM, LopreiatoJO, AladjemMI (2006) Cooperative sequence modules determine replication initiation sites at the human beta-globin locus. Hum Mol Genet 15: 2613–2622.

35. ForresterWC, EpnerE, DriscollMC, EnverT, BriceM, et al. (1990) A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. Genes Dev 4: 1637–1649.

36. GroudineM, Kohwi-ShigematsuT, GelinasR, StamatoyannopoulosG, PapayannopoulouT (1983) Human fetal to adult hemoglobin switching: changes in chromatin structure of the beta-globin gene locus. Proc Natl Acad Sci U S A 80: 7551–7555.

37. FuH, WangL, LinCM, SinghaniaS, BouhassiraEE, et al. (2006) Preventing gene silencing with human replicators. Nat Biotechnol 24: 572–576.

38. TardatM, BrustelJ, KirshO, LefevbreC, CallananM, et al. (2010) The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells. Nat Cell Biol 12: 1086–1093.

39. DellinoGI, CittaroD, PiccioniR, LuziL, BanfiS, et al. (2013) Genome-wide mapping of human DNA-replication origins: levels of transcription at ORC1 sites regulate origin selection and replication timing. Genome Res 23: 1–11.

40. KuoAJ, SongJ, CheungP, Ishibe-MurakamiS, YamazoeS, et al. (2012) The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature 484: 115–119.

41. KloseRJ, GardnerKE, LiangG, Erdjument-BromageH, TempstP, et al. (2007) Demethylation of histone H3K36 and H3K9 by Rph1: a vestige of an H3K9 methylation system in Saccharomyces cerevisiae? Mol Cell Biol 27: 3951–3961.

42. AriasEE, WalterJC (2007) Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev 21: 497–518.

43. DePamphilisML, BlowJJ, GhoshS, SahaT, NoguchiK, et al. (2006) Regulating the licensing of DNA replication origins in metazoa. Curr Opin Cell Biol 18: 231–239.

44. GassenA, BrechtefeldD, SchandryN, Arteaga-SalasJM, IsraelL, et al. (2012) DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei. Nucleic Acids Res 40: 10302–10311.

45. RaynaudC, SozzaniR, GlabN, DomenichiniS, PerennesC, et al. (2006) Two cell-cycle regulated SET-domain proteins interact with proliferating cell nuclear antigen (PCNA) in Arabidopsis. Plant J 47: 395–407.

46. JacobY, StroudH, LeblancC, FengS, ZhuoL, et al. (2010) Regulation of heterochromatic DNA replication by histone H3 lysine 27 methyltransferases. Nature 466: 987–991.

47. ContiC, CaburetS, SchurraC, BensimonA (2001) Molecular combing. Curr Protoc Cytom Chapter 8: Unit 8 10.

48. ContiC, LeoE, EichlerGS, SordetO, MartinMM, et al. (2010) Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res 70: 4470–4480.

49. LangmeadB, SchatzMC, LinJ, PopM, SalzbergSL (2009) Searching for SNPs with cloud computing. Genome Biol 10: R134.

50. RobinsonJT, ThorvaldsdottirH, WincklerW, GuttmanM, LanderES, et al. (2011) Integrative genomics viewer. Nat Biotechnol 29: 24–26.

51. MortazaviA, WilliamsBA, McCueK, SchaefferL, WoldB (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5: 621–628.