The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements

English version České info

Although emerging evidence suggests that transposable elements (TEs) have contributed novel regulatory elements to the human genome, their global impact on transcriptional networks remains largely uncharacterized. Here we show that TEs have contributed to the human genome nearly half of its active elements. Using DNase I hypersensitivity data sets from ENCODE in normal, embryonic, and cancer cells, we found that 44% of open chromatin regions were in TEs and that this proportion reached 63% for primate-specific regions. We also showed that distinct subfamilies of endogenous retroviruses (ERVs) contributed significantly more accessible regions than expected by chance, with up to 80% of their instances in open chromatin. Based on these results, we further characterized 2,150 TE subfamily–transcription factor pairs that were bound in vivo or enriched for specific binding motifs, and observed that TEs contributing to open chromatin had higher levels of sequence conservation. We also showed that thousands of ERV–derived sequences were activated in a cell type–specific manner, especially in embryonic and cancer cells, and we demonstrated that this activity was associated with cell type–specific expression of neighboring genes. Taken together, these results demonstrate that TEs, and in particular ERVs, have contributed hundreds of thousands of novel regulatory elements to the primate lineage and reshaped the human transcriptional landscape.

Vyšlo v časopise: The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements. PLoS Genet 9(5): e32767. doi:10.1371/journal.pgen.1003504
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003504

Souhrn

Zdroje

1. Craig N, R C, M G, AM L (2002) Mobile DNA II. Washington, DC: ASM Press.

2. OrgelLE, CrickFH (1980) Selfish DNA: the ultimate parasite. Nature 284: 604–607.

3. DoolittleWF, SapienzaC (1980) Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601–603.

4. McClintockB (1984) The significance of responses of the genome to challenge. Science 226: 792–801.

5. DavidsonEH, BrittenRJ (1979) Regulation of gene expression: possible role of repetitive sequences. Science 204: 1052–1059.

6. FeschotteC (2008) Transposable elements and the evolution of regulatory networks. Nature reviews Genetics 9: 397–405.

7. BourqueG, LeongB, VegaVB, ChenX, LeeYL, et al. (2008) Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res 18: 1752–1762.

8. WangT, ZengJ, LoweCB, SellersRG, SalamaSR, et al. (2007) Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc Natl Acad Sci U S A 104: 18613–18618.

9. SchmidtD, SchwaliePC, WilsonMD, BallesterB, GoncalvesA, et al. (2012) Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell 148: 335–348.

10. KunarsoG, ChiaNY, JeyakaniJ, HwangC, LuX, et al. (2010) Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42: 631–634.

11. LynchVJ, LeclercRD, MayG, WagnerGP (2011) Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals. Nat Genet 43: 1154–1159.

12. ChuongEB, RumiMA, SoaresMJ, BakerJC (2013) Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nat Genet 45: 325–329.

13. WangJ, ZhuangJ, IyerS, LinX, WhitfieldTW, et al. (2012) Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res 22: 1798–1812.

14. TestoriA, CaizziL, CutrupiS, FriardO, De BortoliM, et al. (2012) The role of Transposable Elements in shaping the combinatorial interaction of Transcription Factors. BMC Genomics 13: 400.

15. Marino-RamirezL, JordanIK (2006) Transposable element derived DNaseI-hypersensitive sites in the human genome. Biology direct 1: 20.

16. WaterstonRH, Lindblad-TohK, BirneyE, RogersJ, AbrilJF, et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

17. EwingAD, KazazianHHJr (2010) High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes. Genome Res 20: 1262–1270.

18. CoufalNG, Garcia-PerezJL, PengGE, YeoGW, MuY, et al. (2009) L1 retrotransposition in human neural progenitor cells. Nature 460: 1127–1131.

19. IskowRC, McCabeMT, MillsRE, ToreneS, PittardWS, et al. (2010) Natural mutagenesis of human genomes by endogenous retrotransposons. Cell 141: 1253–1261.

20. BaillieJK, BarnettMW, UptonKR, GerhardtDJ, RichmondTA, et al. (2011) Somatic retrotransposition alters the genetic landscape of the human brain. Nature 479: 534–537.

21. BernsteinBE, BirneyE, DunhamI, GreenED, GunterC, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.

22. ThurmanRE, RynesE, HumbertR, VierstraJ, MauranoMT, et al. (2012) The accessible chromatin landscape of the human genome. Nature 489: 75–82.

23. CrawfordGE, DavisS, ScacheriPC, RenaudG, HalawiMJ, et al. (2006) DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nature methods 3: 503–509.

24. SaboPJ, KuehnMS, ThurmanR, JohnsonBE, JohnsonEM, et al. (2006) Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nature methods 3: 511–518.

25. DohmJC, LottazC, BorodinaT, HimmelbauerH (2008) Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res 36: e105.

26. NishiharaH, SmitAF, OkadaN (2006) Functional noncoding sequences derived from SINEs in the mammalian genome. Genome Res 16: 864–874.

27. KamalM, XieX, LanderES (2006) A large family of ancient repeat elements in the human genome is under strong selection. Proc Natl Acad Sci U S A 103: 2740–2745.

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

29. LoweCB, KellisM, SiepelA, RaneyBJ, ClampM, et al. (2011) Three periods of regulatory innovation during vertebrate evolution. Science 333: 1019–1024.

30. NephS, VierstraJ, StergachisAB, ReynoldsAP, HaugenE, et al. (2012) An expansive human regulatory lexicon encoded in transcription factor footprints. Nature 489: 83–90.

31. CookM, BuhlingF, AnsorgeS, TatnellPJ, KayJ (2002) Pronapsin A and B gene expression in normal and malignant human lung and mononuclear blood cells. Biochimica et biophysica acta 1577: 10–16.

32. RyanEJ, MarshallAJ, MagalettiD, FloydH, DravesKE, et al. (2002) Dendritic cell-associated lectin-1: a novel dendritic cell-associated, C-type lectin-like molecule enhances T cell secretion of IL-4. Journal of immunology 169: 5638–5648.

33. 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.

34. Marino-RamirezL, LewisKC, LandsmanD, JordanIK (2005) Transposable elements donate lineage-specific regulatory sequences to host genomes. Cytogenetic and genome research 110: 333–341.

35. van de LagemaatLN, LandryJR, MagerDL, MedstrandP (2003) Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends in genetics : TIG 19: 530–536.

36. LamprechtB, WalterK, KreherS, KumarR, HummelM, et al. (2010) Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nature medicine 16: 571–579, 571p following 579.

37. MacfarlanTS, GiffordWD, DriscollS, LettieriK, RoweHM, et al. (2012) Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487: 57–63.

38. JonesPA, BaylinSB (2007) The epigenomics of cancer. Cell 128: 683–692.

39. RoweHM, TronoD (2011) Dynamic control of endogenous retroviruses during development. Virology 411: 273–287.

40. FeschotteC, GilbertC (2012) Endogenous viruses: insights into viral evolution and impact on host biology. Nature reviews Genetics 13: 283–296.

41. KelleyD, RinnJ (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome biology 13: R107.

42. FaulknerGJ, KimuraY, DaubCO, WaniS, PlessyC, et al. (2009) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41: 563–571.

43. Smit A, Hubley, R, Green, P (1996–2012) RepeatMasker Open - 3.0, version 3.2.7. Available: http://www.repeatmasker.org/.

44. KentWJ, SugnetCW, FureyTS, RoskinKM, PringleTH, et al. (2002) The human genome browser at UCSC. Genome Res 12: 996–1006.

45. GlazkoGV, NeiM (2003) Estimation of divergence times for major lineages of primate species. Mol Biol Evol 20: 424–434.

46. GiordanoJ, GeY, GelfandY, AbrusanG, BensonG, et al. (2007) Evolutionary history of mammalian transposons determined by genome-wide defragmentation. PLoS Comput Biol 3: e137 doi:10.1371/journal.pcbi.0030137.

47. 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.

48. RoyS, ErnstJ, KharchenkoPV, KheradpourP, NegreN, et al. (2010) Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330: 1787–1797.

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

50. QuinlanAR, HallIM (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26: 841–842.

51. ChenX, XuH, YuanP, FangF, HussM, et al. (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133: 1106–1117.

52. SandelinA, AlkemaW, EngstromP, WassermanWW, LenhardB (2004) JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res 32: D91–94.

53. MatysV, Kel-MargoulisOV, FrickeE, LiebichI, LandS, et al. (2006) TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 34: D108–110.

54. RobaskyK, BulykML (2011) UniPROBE, update 2011: expanded content and search tools in the online database of protein-binding microarray data on protein-DNA interactions. Nucleic Acids Res 39: D124–128.