Controls of Nucleosome Positioning in the Human Genome

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Nucleosomes are important for gene regulation because their arrangement on the genome can control which proteins bind to DNA. Currently, few human nucleosomes are thought to be consistently positioned across cells; however, this has been difficult to assess due to the limited resolution of existing data. We performed paired-end sequencing of micrococcal nuclease-digested chromatin (MNase–seq) from seven lymphoblastoid cell lines and mapped over 3.6 billion MNase–seq fragments to the human genome to create the highest-resolution map of nucleosome occupancy to date in a human cell type. In contrast to previous results, we find that most nucleosomes have more consistent positioning than expected by chance and a substantial fraction (8.7%) of nucleosomes have moderate to strong positioning. In aggregate, nucleosome sequences have 10 bp periodic patterns in dinucleotide frequency and DNase I sensitivity; and, across cells, nucleosomes frequently have translational offsets that are multiples of 10 bp. We estimate that almost half of the genome contains regularly spaced arrays of nucleosomes, which are enriched in active chromatin domains. Single nucleotide polymorphisms that reduce DNase I sensitivity can disrupt the phasing of nucleosome arrays, which indicates that they often result from positioning against a barrier formed by other proteins. However, nucleosome arrays can also be created by DNA sequence alone. The most striking example is an array of over 400 nucleosomes on chromosome 12 that is created by tandem repetition of sequences with strong positioning properties. In summary, a large fraction of nucleosomes are consistently positioned—in some regions because they adopt favored sequence positions, and in other regions because they are forced into specific arrangements by chromatin remodeling or DNA binding proteins.

Vyšlo v časopise: Controls of Nucleosome Positioning in the Human Genome. PLoS Genet 8(11): e32767. doi:10.1371/journal.pgen.1003036
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003036

Souhrn

Zdroje

1. KornbergRD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184: 868–871.

2. KornbergRD, LorchY (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98: 285–294.

3. JohnS, SaboPJ, ThurmanRE, SungMH, BiddieSC, et al. (2011) Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat Genet 43: 264–8.

4. KaplanT, LiXY, SaboPJ, ThomasS, StamatoyannopoulosJA, et al. (2011) Quantitative Models of the Mechanisms That Control Genome-Wide Patterns of Transcription Factor Binding during Early Drosophila Development. PLoS Genet 7: e1001290 doi:10.1371/journal.pgen.1001290.

5. AlbertI, MavrichTN, TomshoLP, QiJ, ZantonSJ, et al. (2007) Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature 446: 572–576.

6. KaplanN, HughesTR, LiebJD, WidomJ, SegalE (2010) Contribution of histone sequence preferences to nucleosome organization: proposed definitions and methodology. Genome Biol 11: 140.

7. LowaryPT, WidomJ (1998) New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J Mol Biol 276: 19–42.

8. ThåströmA, LowaryPT, WidlundHR, CaoH, KubistaM, et al. (1999) Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences. J Mol Biol 288: 213–229.

9. IyerV, StruhlK (1995) Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. EMBO J 14: 2570–2579.

10. StruhlK (1985) Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. Proc Natl Acad Sci USA 82: 8419–8423.

11. YuanGC, LiuYJ, DionMF, SlackMD, WuLF, et al. (2005) Genome-scale identification of nucleosome positions in S. cerevisiae. Science 309: 626–630.

12. FieldY, KaplanN, Fondufe-MittendorfY, MooreIK, SharonE, et al. (2008) Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLoS Comput Biol 4: e1000216 doi:10.1371/journal.pcbi.1000216.

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

14. ValouevA, JohnsonSM, BoydSD, SmithCL, FireAZ, et al. (2011) Determinants of nucleosome organization in primary human cells. Nature 474: 516–520.

15. SatchwellSC, DrewHR, TraversAA (1986) Sequence periodicities in chicken nucleosome core DNA. J Mol Biol 191: 659–675.

16. SegalE, Fondufe-MittendorfY, ChenL, ThåströmA, FieldY, et al. (2006) A genomic code for nucleosome positioning. Nature 442: 772–778.

17. WidlundHR, CaoH, SimonssonS, MagnussonE, SimonssonT, et al. (1997) Identification and characterization of genomic nucleosome-positioning sequences. J Mol Biol 267: 807–817.

18. MavrichTN, JiangC, IoshikhesIP, LiX, VentersBJ, et al. (2008) Nucleosome organization in the Drosophila genome. Nature 453: 358–362.

19. MavrichTN, IoshikhesIP, VentersBJ, JiangC, TomshoLP, et al. (2008) A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res 18: 1073–1083.

20. WassonT, HarteminkAJ (2009) An ensemble model of competitive multi-factor binding of the genome. Genome Res 19: 2101–2112.

21. CairnsBR (2009) The logic of chromatin architecture and remodelling at promoters. Nature 461: 193–198.

22. KornbergRD, StryerL (1988) Statistical distributions of nucleosomes: nonrandom locations by a stochastic mechanism. Nucleic Acids Research 16: 6677–6690.

23. SchonesDE, CuiK, CuddapahS, RohTY, BarskiA, et al. (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132: 887–898.

24. ZhangY, MoqtaderiZ, RattnerBP, EuskirchenG, SnyderM, et al. (2009) Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat Struct Mol Biol 16: 847–852.

25. SasakiS, MelloCC, ShimadaA, NakataniY, HashimotoSI, et al. (2009) Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites. Science 323: 401–4.

26. FuY, SinhaM, PetersonCL, WengZ (2008) The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome. PLoS Genet 4: e1000138 doi:10.1371/journal.pgen.1000138.

27. KaplanN, MooreI, Fondufe-MittendorfY, GossettAJ, TilloD, et al. (2010) Nucleosome sequence preferences influence in vivo nucleosome organization. Nat Struct Mol Biol 17: 918–20 author reply 920–2.

28. ENCODE Project Consortium (2011) MyersRM, StamatoyannopoulosJ, SnyderM, DunhamI, et al. (2011) A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 9: e1001046 doi:10.1371/journal.pbio.1001046.

29. Pique-RegiR, DegnerJF, PaiAA, GaffneyDJ, GiladY, et al. (2011) Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data. Genome Res 21: 447–55.

30. DegnerJF, PaiAA, Pique-RegiR, VeyrierasJB, GaffneyDJ, et al. (2012) DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482: 390–394.

31. Genomes Project Consortium (2010) DurbinRM, AbecasisGR, AltshulerDL, AutonA, et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467: 1061–1073.

32. NollM (1974) Subunit structure of chromatin. Nature 251: 249–251.

33. KaplanN, MooreIK, Fondufe-MittendorfY, GossettAJ, TilloD, et al. (2009) The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458: 362–366.

34. BoyleAP, DavisS, ShulhaHP, MeltzerP, MarguliesEH, et al. (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell 132: 311–322.

35. CousinsDJ, IslamSA, SandersonMR, ProykovaYG, Crane-RobinsonC, et al. (2004) Redefinition of the cleavage sites of DNase I on the nucleosome core particle. J Mol Biol 335: 1199–1211.

36. KlugA, LutterLC (1981) The helical periodicity of DNA on the nucleosome. Nucleic Acids Research 9: 4267–4283.

37. LutterLC (1979) Precise location of DNase I cutting sites in the nucleosome core determined by high resolution gel electrophoresis. Nucleic Acids Research 6: 41–56.

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

39. BensonG (1999) Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Research 27: 573–580.

40. KundajeA, Kyriazopoulou-PanagiotopoulouS, LibbrechtM, SmithCL, RahaD, et al. (2012) Ubiquitous heterogeneity and asymmetry of the chromatin environment at regulatory elements. Genome Res 22: 1735–1747.

41. LaiWK, BuckMJ (2010) ArchAlign: coordinate-free chromatin alignment reveals novel architectures. Genome Biol 11: R126.

42. TilloD, KaplanN, MooreIK, Fondufe-MittendorfY, GossettAJ, et al. (2010) High nucleosome occupancy is encoded at human regulatory sequences. PLoS ONE 5: e9129 doi:10.1371/journal.pone.0009129.

43. PenningsS, MeerssemanG, BradburyEM (1991) Mobility of positioned nucleosomes on 5 S rDNA. J Mol Biol 220: 101–110.

44. DongF, HansenJC, Van HoldeKE (1990) DNA and protein determinants of nucleosome positioning on sea urchin 5S rRNA gene sequences in vitro. Proc Natl Acad Sci USA 87: 5724–5728.

45. ValouevA, IchikawaJ, TonthatT, StuartJ, RanadeS, et al. (2008) A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res 18: 1051–1063.

46. BrogaardK, LiqunX, WangJP, WidomJ (2012) A base pair resolution map of nucleosome positions in yeast. Nature 486: 496–501.

47. ZhangZ, WippoCJ, WalM, WardE, KorberP, et al. (2011) A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science 332: 977–980.

48. GkikopoulosT, SchofieldP, SinghV, PinskayaM, MellorJ, et al. (2011) A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome Organization. Science 333: 1758–1760.

49. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.

50. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079.

51. ChungHR, DunkelI, HeiseF, LinkeC, KrobitschS, et al. (2010) The effect of micrococcal nuclease digestion on nucleosome positioning data. PLoS ONE 5: e15754 doi:10.1371/journal.pone.0015754.

52. DingwallC, LomonossoffGP, LaskeyRA (1981) High sequence specificity of micrococcal nuclease. Nucleic Acids Research 9: 2659–2673.

53. AllanJ, FraserRM, Owen-HughesT, Keszenman-PereyraD (2012) Micrococcal nuclease does not substantially bias nucleosome mapping. J Mol Biol 417: 152–164.

54. PickrellJK, GaffneyDJ, GiladY, PritchardJK (2011) False positive peaks in ChIP-seq and other sequencing-based functional assays caused by unannotated high copy number regions. Bioinformatics 27: 2144–2146.

55. StoreyJD, TibshiraniR (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci USA 100: 9440–9445.

56. ZhangY, LiuT, MeyerCA, EeckhouteJ, JohnsonDS, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9: R137.

57. GuanY, StephensM (2008) Practical issues in imputation-based association mapping. PLoS Genet 4: e1000279 doi:10.1371/journal.pgen.1000279.

58. ScheetP, StephensM (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78: 629–644.