The Spatiotemporal Program of DNA Replication Is Associated with Specific Combinations of Chromatin Marks in Human Cells


Replication is the mechanism by which genomes are duplicated into two exact copies. Genomic stability is under the control of a spatiotemporal program that orchestrates both the positioning and the timing of firing of about 50,000 replication starting points, also called replication origins. Replication bubbles found at origins have been very difficult to map due to their short lifespan. Moreover, with the flood of data characterizing new sequencing technologies, the precise statistical analysis of replication data has become an additional challenge. We propose a new method to map replication origins on the human genome, and we assess the reliability of our finding using experimental validation and comparison with origins maps obtained by bubble trapping. This fine mapping then allowed us to identify potential regulators of the replication dynamics. Our study highlights the key role of CpG Islands and identifies new potential epigenetic regulators (methylation of lysine 4 on histone H4, and tri-methylation of lysine 27 on histone H3) whose coupling is correlated with an increase in the efficiency of replication origins, suggesting those marks as potential key regulators of replication. Overall, our study defines new potentially important pathways that might regulate the sequential firing of origins during genome duplication.


Vyšlo v časopise: The Spatiotemporal Program of DNA Replication Is Associated with Specific Combinations of Chromatin Marks in Human Cells. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004282
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004282

Souhrn

Replication is the mechanism by which genomes are duplicated into two exact copies. Genomic stability is under the control of a spatiotemporal program that orchestrates both the positioning and the timing of firing of about 50,000 replication starting points, also called replication origins. Replication bubbles found at origins have been very difficult to map due to their short lifespan. Moreover, with the flood of data characterizing new sequencing technologies, the precise statistical analysis of replication data has become an additional challenge. We propose a new method to map replication origins on the human genome, and we assess the reliability of our finding using experimental validation and comparison with origins maps obtained by bubble trapping. This fine mapping then allowed us to identify potential regulators of the replication dynamics. Our study highlights the key role of CpG Islands and identifies new potential epigenetic regulators (methylation of lysine 4 on histone H4, and tri-methylation of lysine 27 on histone H3) whose coupling is correlated with an increase in the efficiency of replication origins, suggesting those marks as potential key regulators of replication. Overall, our study defines new potentially important pathways that might regulate the sequential firing of origins during genome duplication.


Zdroje

1. CadoretJC, MeischF, Hassan-ZadehV, LuytenI, GuilletC, et al. (2008) Genome-wide studies highlight indirect links between human replication origins and gene regulation. Proc Natl Acad Sci USA 105: 15837–15842.

2. CayrouC, GregoireD, CoulombeP, DanisE, MechaliM (2012) Genome-scale identification of active DNA replication origins. Methods 57: 158–164.

3. GerbiSA, BielinskyAK (1997) Replication initiation point mapping. Methods 13: 271–280.

4. LucasI, PalakodetiA, JiangY, YoungDJ, JiangN, et al. (2007) High-throughput mapping of origins of replication in human cells. EMBO Rep 8: 770–777.

5. CadoretJC, PrioleauMN (2010) Genome-wide approaches to determining origin distribution. Chromosome Res 18: 79–89.

6. KarnaniN, TaylorCM, MalhotraA, DuttaA (2010) Genomic study of replication initiation in human chromosomes reveals the inuence of transcription regulation and chromatin structure on origin selection. Mol Biol Cell 21: 393–404.

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

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

9. BlahnikKR, DouL, O'GeenH, McPhillipsT, XuX, et al. (2010) Sole-Search: an integrated analysis program for peak detection and functional annotation using ChIP-seq data. Nucleic Acids Res 38: e13.

10. 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.

11. MesnerLD, ValsakumarV, CieslikM, PickinR, HamlinJL, et al. (2013) Bubble-seq analysis of the human genome reveals distinct chromatin-mediated mechanisms for regulating early- and late-firing origins. Genome Res 23: 1774–1788.

12. 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.

13. ThurmanRE, DayN, NobleWS, StamatoyannopoulosJA (2007) Identification of higher-order functional domains in the human ENCODE regions. Genome Res 17: 917–927.

14. ChandraT, KirschnerK, ThuretJY, PopeBD, RybaT, et al. (2012) Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol Cell 47: 203–214.

15. ChanH, ZhangN (2007) Scan statistics with weighted observations. Journal of the American Statistical Association 102: 595–602.

16. 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.

17. Sequeira-MendesJ, Diaz-UriarteR, ApedaileA, HuntleyD, BrockdorffN, et al. (2009) Tran-scription initiation activity sets replication origin efficiency in mammalian cells. PLoS Genet 5: e1000446.

18. CayrouC, CoulombeP, PuyA, RialleS, KaplanN, et al. (2012) New insights into replication origin characteristics in metazoans. Cell Cycle 11: 658–667.

19. ChenCL, RappaillesA, DuquenneL, HuvetM, GuilbaudG, et al. (2010) Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes. Genome Res 20: 447–457.

20. GuilbaudG, RappaillesA, BakerA, ChenCL, ArneodoA, et al. (2011) Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome. PLoS Comput Biol 7: e1002322.

21. HansenRS, ThomasS, SandstromR, CanfieldTK, ThurmanRE, et al. (2010) Sequencing newly replicated DNA reveals widespread plasticity in human replication timing. Proc Natl Acad Sci USA 107: 139–144.

22. ErnstJ, KheradpourP, MikkelsenTS, ShoreshN, WardLD, et al. (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473: 43–49.

23. NecsuleaA, GuilletC, CadoretJC, PrioleauMN, DuretL (2009) The relationship between DNA replication and human genome organization. Mol Biol Evol 26: 729–741.

24. GeXQ, JacksonDA, BlowJJ (2007) Dormant origins licensed by excess Mcm2–7 are required for human cells to survive replicative stress. Genes Dev 21: 3331–3341.

25. IbarraA, SchwobE, MendezJ (2008) Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proc Natl Acad Sci USA 105: 8956–8961.

26. ValtonAL, Hassan-ZadehV, LemaI, BoggettoN, AlbertiP, et al. (2014) G4 motifs affect origin positioning and efficiency in two vertebrate replicators. EMBO J in press.

27. AuditB, BakerA, ChenCL, RappaillesA, GuilbaudG, et al. (2013) Multiscale analysis of genome-wide replication timing profiles using a wavelet-based signal-processing algorithm. Nat Protoc 8: 98–110.

28. AuditB, ZaghloulL, VaillantC, ChevereauG, d'Aubenton CarafaY, et al. (2009) Open chromatin encoded in DNA sequence is the signature of ‘master’ replication origins in human cells. Nucleic Acids Res 37: 6064–6075.

29. HamlinJL, MesnerLD, LarO, TorresR, ChodaparambilSV, et al. (2008) A revisionist replicon model for higher eukaryotic genomes. J Cell Biochem 105: 321–329.

30. McNairnAJ, GilbertDM (2003) Epigenomic replication: linking epigenetics to DNA replication. Bioessays 25: 647–656.

31. GayS, LachagesAM, MillotGA, CourbetS, LetessierA, et al. (2010) Nucleotide supply, not local histone acetylation, sets replication origin usage in transcribed regions. EMBO Rep 11: 698–704.

32. PrioleauMN, GendronMC, HyrienO (2003) Replication of the chicken beta-globin locus: early- firing origins at the 5′ HS4 insulator and the rho- and betaA-globin genes show opposite epigenetic modifications. Mol Cell Biol 23: 3536–3549.

33. HirataniI, RybaT, ItohM, YokochiT, SchwaigerM, et al. (2008) Global reorganization of repli-cation domains during embryonic stem cell differentiation. PLoS Biol 6: e245.

34. 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.

35. BeckDB, BurtonA, OdaH, Ziegler-BirlingC, Torres-PadillaME, et al. (2012) The role of PR-Set7 in replication licensing depends on Suv4-20h. Genes Dev 26: 2580–2589.

36. GorenA, TabibA, HechtM, CedarH (2008) DNA replication timing of the human beta-globin domain is controlled by histone modification at the origin. Genes Dev 22: 1319–1324.

37. Hassan-ZadehV, ChilakaS, CadoretJC, MaMK, BoggettoN, et al. (2012) USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator. PLoS Biol 10: e1001277.

38. EatonML, PrinzJA, MacAlpineHK, TretyakovG, KharchenkoPV, et al. (2011) Chromatin signatures of the Drosophila replication program. Genome Res 21: 164–174.

39. Lo SardoF, LanzuoloC, ComoglioF, De BardiM, ParoR, et al. (2013) PcG-mediated higher-order chromatin structures modulate replication programs at the Drosophila BX-C. PLoS Genet 9: e1003283.

40. AotoT, SaitohN, SakamotoY, WatanabeS, NakaoM (2008) Polycomb group protein-associated chromatin is reproduced in post-mitotic G1 phase and is required for S phase progression. J Biol Chem 283: 18905–18915.

41. PosfaiE, KunzmannR, BrochardV, SalvaingJ, CabuyE, et al. (2012) Polycomb function during oogenesis is required for mouse embryonic development. Genes Dev 26: 920–932.

42. PicardF, RobinS, LavielleM, VaisseC, DaudinJJ (2005) A statistical approach for array CGH data analysis. BMC Bioinformatics 6: 27.

43. HuppertJL, BalasubramanianS (2005) Prevalence of quadruplexes in the human genome. Nucleic Acids Res 33: 2908–2916.

44. BakerA, AuditB, ChenCL, MoindrotB, LeleuA, et al. (2012) Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines. PLoS Comput Biol 8: e1002443.

45. AbecasisGR (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491: 56–65.

46. Le CaoKA, BoitardS, BesseP (2011) Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems. BMC Bioinformatics 12: 253.

47. GiardineB, RiemerC, HardisonRC, BurhansR, ElnitskiL, et al. (2005) Galaxy: a platform for interactive large-scale genome analysis. Genome Res 15: 1451–1455.

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Genetika Reprodukčná medicína

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PLOS Genetics


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