SNF5 Is an Essential Executor of Epigenetic Regulation during Differentiation

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Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs) at the regulatory sites of OCT4 repressed target genes such as PAX6 and NEUROG1, which are crucial for cell fate determination. Concurrently, SNF5 closes the NDRs at the regulatory regions of OCT4-activated target genes such as OCT4 itself and NANOG. Furthermore, using loss -⁠ and gain-of-function experiments followed by extensive genome-wide analyses including gene expression microarrays and ChIP-sequencing, we highlight that SNF5 plays dual roles during differentiation by antagonizing the expression of genes that were either activated or repressed by OCT4, respectively. Together, we demonstrate that SNF5 executes the switch between pluripotency and differentiation.

Vyšlo v časopise: SNF5 Is an Essential Executor of Epigenetic Regulation during Differentiation. PLoS Genet 9(4): e32767. doi:10.1371/journal.pgen.1003459
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003459

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Zdroje

1. HochedlingerK, PlathK (2009) Epigenetic reprogramming and induced pluripotency. Development 136 : 509–523.

2. ReikW (2007) Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447 : 425–432.

3. SharmaS, KellyTK, JonesPA (2010) Epigenetics in cancer. Carcinogenesis 31 : 27–36.

4. NatarajanA, YardimciGG, SheffieldNC, CrawfordGE, OhlerU (2012) Predicting cell-type-specific gene expression from regions of open chromatin. Genome Res 22 : 1711–1722.

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

6. JaenischR, YoungR (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132 : 567–582.

7. YoungR (2011) Control of the Embryonic Stem Cell State. Cell 144 : 940–954.

8. HengJC, FengB, HanJ, JiangJ, KrausP, et al. (2010) The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 6 : 167–174.

9. PardoM, LangB, YuL, ProsserH, BradleyA, et al. (2010) An expanded Oct4 interaction network: implications for stem cell biology, development, and disease. Cell Stem Cell 6 : 382–395.

10. van den BergDL, SnoekT, MullinNP, YatesA, BezstarostiK, et al. (2010) An Oct4-centered protein interaction network in embryonic stem cells. Cell Stem Cell 6 : 369–381.

11. DingJ, XuH, FaiolaF, Ma'ayanA, WangJ (2011) Oct4 links multiple epigenetic pathways to the pluripotency network. Cell Res 22 : 155–167.

12. LorchY, LaPointeJW, KornbergRD (1987) Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones. Cell 49 : 203–210.

13. JiangC, PughBF (2009) Nucleosome positioning and gene regulation: advances through genomics. Nat Rev Genet 10 : 161–172.

14. ChodavarapuRK, FengS, BernatavichuteYV, ChenPY, StroudH, et al. (2010) Relationship between nucleosome positioning and DNA methylation. Nature

15. HeHH, MeyerCA, ShinH, BaileyST, WeiG, et al. (2010) Nucleosome dynamics define transcriptional enhancers. Nat Genet 42 : 343–347.

16. SchonesDE, CuiK, CuddapahS, RohT-Y, BarskiA, et al. (2008) Dynamic Regulation of Nucleosome Positioning in the Human Genome. Cell 132 : 887–898.

17. SegalE, WidomJ (2009) What controls nucleosome positions? Trends Genet 25 : 335–343.

18. ZhangZ, WippoCJ, WalM, WardE, KorberP, et al. (2011) A Packing Mechanism for Nucleosome Organization Reconstituted Across a Eukaryotic Genome. Science 332 : 977–980.

19. YouJS, KellyTK, De CarvalhoDD, TaberlayPC, LiangG, et al. (2011) OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes. Proc Natl Acad Sci U S A 108 : 14497–14502.

20. GaffneyDJ, McVickerG, PaiAA, Fondufe-MittendorfYN, LewellenN, et al. (2012) Controls of nucleosome positioning in the human genome. PLoS Genet 8: e1003036 doi:10.1371/journal.pgen.1003036.

21. KellyTK, MirandaTB, LiangG, BermanBP, LinJC, et al. (2010) H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes. Mol Cell 39 : 901–911.

22. TaberlayPC, KellyTK, LiuC-C, YouJS, De CarvalhoDD, et al. (2011) Polycomb-Repressed Genes Have Permissive Enhancers that Initiate Reprogramming. Cell 147 : 1283–1294.

23. Andreu-VieyraC, LaiJ, BermanBP, FrenkelB, JiaL, et al. (2011) Dynamic nucleosome-depleted regions at androgen receptor enhancers in the absence of ligand in prostate cancer cells. Mol Cell Biol 31 : 4648–4662.

24. HargreavesDC, CrabtreeGR (2011) ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res 21 : 396–420.

25. HoL, CrabtreeGR (2010) Chromatin remodelling during development. Nature 463 : 474–484.

26. KidderBL, PalmerS, KnottJG (2009) SWI/SNF-Brg1 Regulates Self-Renewal and Occupies Core Pluripotency-Related Genes in Embryonic Stem Cells. Stem Cells 27 : 317–328.

27. SinghalN, GraumannJ, WuG, Ara?o-BravoMJ, HanDW, et al. (2010) Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming. Cell 141 : 943–955.

28. ChaiB, HuangJ, CairnsBR, LaurentBC (2005) Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. Genes Dev 19 : 1656–1661.

29. PedersenTA, Kowenz-LeutzE, LeutzA, NerlovC (2001) Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation. Genes Dev 15 : 3208–3216.

30. Ramirez-CarrozziVR, NazarianAA, LiCC, GoreSL, SridharanR, et al. (2006) Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev 20 : 282–296.

31. ReismanD, GlarosS, ThompsonEA (2009) The SWI/SNF complex and cancer. Oncogene 28 : 1653–1668.

32. WilsonBG, RobertsCWM (2011) SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 11 : 481–492.

33. YouJS, JonesPA (2012) Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22 : 9–20.

34. DawsonMA, KouzaridesT (2012) Cancer epigenetics: from mechanism to therapy. Cell 150 : 12–27.

35. KimJH, SarafA, FlorensL, WashburnM, WorkmanJL (2010) Gcn5 regulates the dissociation of SWI/SNF from chromatin by acetylation of Swi2/Snf2. Genes Dev 24 : 2766–2771.

36. SifS, StukenbergPT, KirschnerMW, KingstonRE (1998) Mitotic inactivation of a human SWI/SNF chromatin remodeling complex. Genes Dev 12 : 2842–2851.

37. RobertsCW, BiegelJA (2009) The role of SMARCB1/INI1 in development of rhabdoid tumor. Cancer Biol Ther 8 : 412–416.

38. JaganiZ, Mora-BlancoEL, SansamCG, McKennaES, WilsonB, et al. (2010) Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Nat Med 16 : 1429–1433.

39. IsakoffMS, SansamCG, TamayoP, SubramanianA, EvansJA, et al. (2005) Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc Natl Acad Sci U S A 102 : 17745–17750.

40. GuidiCJ, MudhasaniR, HooverK, KoffA, LeavI, et al. (2006) Functional Interaction of the Retinoblastoma and Ini1/Snf5 Tumor Suppressors in Cell Growth and Pituitary Tumorigenesis. Cancer Research 66 : 8076–8082.

41. WilsonBG, WangX, ShenX, McKennaES, LemieuxME, et al. (2010) Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18 : 316–328.

42. GaoX, TateP, HuP, TjianR, SkarnesWC, et al. (2008) ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a. Proc Natl Acad Sci U S A 105 : 6656–6661.

43. HoL, JothiR, RonanJL, CuiK, ZhaoK, et al. (2009) An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network. Proc Natl Acad Sci U S A 106 : 5187–5191.

44. HoL, RonanJL, WuJ, StaahlBT, ChenL, et al. (2009) An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proc Natl Acad Sci U S A 106 : 5181–5186.

45. YanZ, WangZ, SharovaL, SharovAA, LingC, et al. (2008) BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells 26 : 1155–1165.

46. HirabayashiY, GotohY (2010) Epigenetic control of neural precursor cell fate during development. Nat Rev Neurosci 11 : 377–388.

47. ZhangX, HuangCT, ChenJ, PankratzMT, XiJ, et al. (2010) Pax6 Is a Human Neuroectoderm Cell Fate Determinant. Cell Stem Cell 7 : 90–100.

48. DamjanovI, HorvatB, GibasZ (1993) Retinoic acid-induced differentiation of the developmentally pluripotent human germ cell tumor-derived cell line, NCCIT. Lab Invest 68 : 220–232.

49. BoyerLA, PlathK, ZeitlingerJ, BrambrinkT, MedeirosLA, et al. (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441 : 349–353.

50. CaoR, ZhangY (2004) The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Current Opinion in Genetics & Development 14 : 155–164.

51. Ben-PorathI, ThomsonMW, CareyVJ, GeR, BellGW, et al. (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40 : 499–507.

52. HoL, MillerEL, RonanJL, HoWQ, JothiR, et al. (2011) esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function. Nat Cell Biol 13 : 903–913.

53. MyantK, TermanisA, SundaramAY, BoeT, LiC, et al. (2011) LSH and G9a/GLP complex are required for developmentally programmed DNA methylation. Genome Res 21 : 83–94.

54. HockH (2012) A complex Polycomb issue: the two faces of EZH2 in cancer. Genes Dev 26 : 751–755.

55. RobertsCW, GalushaSA, McMenaminME, FletcherCD, OrkinSH (2000) Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci U S A 97 : 13796–13800.

56. PhelanML, SifS, NarlikarGJ, KingstonRE (1999) Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell 3 : 247–253.

57. DoanDN, VealTM, YanZ, WangW, JonesSN, et al. (2004) Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI//SNF enzymes. Oncogene 23 : 3462–3473.

58. EuskirchenGM, AuerbachRK, DavidovE, GianoulisTA, ZhongG, et al. (2011) Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches. PLoS Genet 7: e1002008 doi:10.1371/journal.pgen.1002008.

59. ImbalzanoAN, KwonH, GreenMR, KingstonRE (1994) Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature 370 : 481–485.

60. KwonH, ImbalzanoAN, KhavariPA, KingstonRE, GreenMR (1994) Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature 370 : 477–481.

61. SchwabishMA, StruhlK (2007) The Swi/Snf complex is important for histone eviction during transcriptional activation and RNA polymerase II elongation in vivo. Mol Cell Biol 27 : 6987–6995.

62. ThompsonCM, KoleskeAJ, ChaoDM, YoungRA (1993) A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast. Cell 73 : 1361–1375.

63. LessardJ, WuJI, RanishJA, WanM, WinslowMM, et al. (2007) An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55 : 201–215.

64. KuM, KocheRP, RheinbayE, MendenhallEM, EndohM, et al. (2008) Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 4: e1000242 doi:10.1371/journal.pgen.1000242.

65. DuP, KibbeWA, LinSM (2008) lumi: a pipeline for processing Illumina microarray. Bioinformatics 24 : 1547–1548.

66. SmythGK, MichaudJ, ScottHS (2005) Use of within-array replicate spots for assessing differential expression in microarray experiments. Bioinformatics 21 : 2067–2075.

67. SmythGK, SpeedT (2003) Normalization of cDNA microarray data. Methods 31 : 265–273.

68. KimJ, WooAJ, ChuJ, SnowJW, FujiwaraY, et al. (2010) A Myc Network Accounts for Similarities between Embryonic Stem and Cancer Cell Transcription Programs. Cell 143 : 313–324.

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