#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements


Polycomb Group (PcG) proteins are epigenetic repressors essential for development and cell differentiation. PcG proteins form five complexes targeted to specific genes by Polycomb Response Elements (PREs). How PcG complexes are recruited to PREs is poorly understood. Here we investigate the recruitment of PhoRC, a seemingly simple case of a complex that contains a sequence-specific DNA binding subunit: PHO (or the related protein PHOL). Unexpectedly, we find that the sequence specific binding of PHO is not a primary determinant for recruitment of PhoRC to PRE, which depends on the non-DNA binding subunit SFMBT and cross-talk with another PcG complex, PRC1. The binding of PhoRC is helped by PRC1 and, in turn, may stabilize the binding of PRC1. We propose that the recruitment based on combinatorial interactions enables the conditional binding of PcG proteins, which is important for switching the state of the target genes from repressed to active. The critical role of the cross-talk between PhoRC and PRC1 is further supported by the finding that in mammals, where the protein domains linking the two complexes are missing, the PHO ortholog YY1 has no implication in PcG repression, despite 100% conservation between DNA binding domains of YY1 and PHO.


Vyšlo v časopise: Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004495
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004495

Souhrn

Polycomb Group (PcG) proteins are epigenetic repressors essential for development and cell differentiation. PcG proteins form five complexes targeted to specific genes by Polycomb Response Elements (PREs). How PcG complexes are recruited to PREs is poorly understood. Here we investigate the recruitment of PhoRC, a seemingly simple case of a complex that contains a sequence-specific DNA binding subunit: PHO (or the related protein PHOL). Unexpectedly, we find that the sequence specific binding of PHO is not a primary determinant for recruitment of PhoRC to PRE, which depends on the non-DNA binding subunit SFMBT and cross-talk with another PcG complex, PRC1. The binding of PhoRC is helped by PRC1 and, in turn, may stabilize the binding of PRC1. We propose that the recruitment based on combinatorial interactions enables the conditional binding of PcG proteins, which is important for switching the state of the target genes from repressed to active. The critical role of the cross-talk between PhoRC and PRC1 is further supported by the finding that in mammals, where the protein domains linking the two complexes are missing, the PHO ortholog YY1 has no implication in PcG repression, despite 100% conservation between DNA binding domains of YY1 and PHO.


Zdroje

1. MoreyL, HelinK (2010) Polycomb group protein-mediated repression of transcription. Trends Biochem Sci 35: 323–332.

2. MüllerJ, VerrijzerP (2009) Biochemical mechanisms of gene regulation by polycomb group protein complexes. Curr Opin Genet Dev 19: 150–158.

3. SimonJA, KingstonRE (2009) Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 10: 697–708.

4. SchwartzYB, PirrottaV (2007) Polycomb silencing mechanisms and the management of genomic programmes. Nat Rev Genet 8: 9–22.

5. CzerminB, MelfiR, McCabeD, SeitzV, ImhofA, PirrottaV (2002) Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111: 185–196.

6. MüllerJ, HartCM, FrancisNJ, VargasML, SenguptaA, et al. (2002) Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111: 197–208.

7. CaoR, WangL, WangH, XiaL, Erdjument-BromageH, et al. (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298: 1039–1043.

8. KuzmichevA, NishiokaK, Erdjument-BromageH, TempstP, ReinbergD (2002) Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev 16: 2893–2905.

9. WangH, WangL, Erdjument-BromageH, VidalM, TempstP, et al. (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431: 873–878.

10. ElderkinS, MaertensGN, EndohM, MalleryDL, MorriceN, et al. (2007) A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin. Mol Cell 28: 107–120.

11. KlymenkoT, PappB, FischleW, KöcherT, SchelderM, et al. (2006) A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities. Genes Dev 20: 1110–1122.

12. LagarouA, Mohd-SaripA, MoshkinYM, ChalkleyGE, BezstarostiK, et al. (2008) dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing. Genes Dev 22: 2799–2810.

13. ScheuermannJC, de Ayala AlonsoAG, OktabaK, Ly-HartigN, McGintyRK, et al. (2010) Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465: 243–247.

14. MüllerJ, KassisJA (2006) Polycomb response elements and targeting of Polycomb group proteins in Drosophila. Curr Opin Genet Dev 16: 476–484.

15. SchwartzYB, PirrottaV (2008) Polycomb complexes and epigenetic states. Curr Opin Cell Biol 20: 266–273.

16. FritschC, BrownJL, KassisJA, MullerJ (1999) The DNA-binding Polycomb group protein Pleiohomeotic mediates silencing of a Drosophila homeotic gene. Development 126: 3905–3913.

17. MishraRK, MihalyJ, BargesS, SpiererA, KarchF, et al. (2001) The iab-7 polycomb response element maps to a nucleosome-free region of chromatin and requires both GAGA and pleiohomeotic for silencing activity. Mol Cell Biol 21: 1311–1318.

18. BrownJL, FritschC, MullerJ, KassisJA (2003) The Drosophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing. Development 130: 285–294.

19. WangL, BrownJL, CaoR, ZhangY, KassisJA, et al. (2004) Hierarchical recruitment of polycomb group silencing complexes. Mol Cell 14: 637–646.

20. SchwartzYB, KahnTG, NixDA, LiXY, BourgonR, et al. (2006) Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet 38: 700–705.

21. KahnTG, SchwartzYB, DellinoGI, PirrottaV (2006) Polycomb complexes and the propagation of the methylation mark at the Drosophila ubx gene. J Biol Chem 281: 29064–29075.

22. PappB, MullerJ (2006) Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins. Genes Dev 20: 2041–2054.

23. SchwartzYB, KahnTG, StenbergP, OhnoK, BourgonR, et al. (2010) Alternative epigenetic chromatin states of polycomb target genes. PLoS Genet 6: e1000805.

24. KimJD, FaulkC, KimJ (2007) Retroposition and evolution of the DNA-binding motifs of YY1, YY2 and REX1. Nucleic Acids Res 35: 3442–3452.

25. SchuettengruberB, GanapathiM, LeblancB, PortosoM, JaschekR, et al. (2009) Functional anatomy of polycomb and trithorax chromatin landscapes in Drosophila embryos. PLoS Biol 7: e13.

26. CaiY, JinJ, YaoT, GottschalkAJ, SwansonSK, et al. (2007) YY1 functions with INO80 to activate transcription. Nat Struct Mol Biol 14: 872–874.

27. Hyde-DeRuyscherRP, JenningsE, ShenkT (1995) DNA binding sites for the transcriptional activator/repressor YY1. Nucleic Acids Res 23: 4457–65.

28. KimJD, KimJ (2009) YY1's longer DNA-binding motifs. Genomics 93: 152–158.

29. OktabaK, GutiérrezL, GagneurJ, GirardotC, SenguptaAK, et al. (2008) Dynamic regulation by polycomb group protein complexes controls pattern formation and the cell cycle in Drosophila. Dev Cell 15: 877–889.

30. KwongC, AdryanB, BellI, MeadowsL, RussellS, et al. (2008) Stability and dynamics of polycomb target sites in Drosophila development. PLoS Genet 4 (9) e1000178.

31. CunninghamMD, BrownJL, KassisJA (2010) Characterization of the Polycomb Group Response Elements of the Drosophila melanogaster invected locus. Mol Cell Biol 30: 820–828.

32. CherbasL, WillinghamA, ZhangD, YangL, ZouY, et al. (2011) The transcriptional diversity of 25 Drosophila cell lines. Genome Res 21: 301–14.

33. GrimmC, MatosR, Ly-HartigN, SteuerwaldU, LindnerD, et al. (2009) Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt. EMBO J 28: 1965–1977.

34. SimcoxA, MitraS, TruesdellS, PaulL, ChenT, et al. (2008) Efficient Genetic Method for Establishing Drosophila Cell Lines Unlocks the Potential to Create Lines of Specific Genotypes. PloS Genet 4 (8) e1000142.

35. WuCT, HoweM (1995) A Genetic Analysis of the Suppressor 2 of Zeste Complex of Drosophila Melanogaster. Genetics 140: 139–181.

36. MarchettiM, FantiL, BerlocoM, PimpinelliS (2003) Differential expression of the Drosophila BX-C in polytene chromosomes in cells of larval fat bodies: a cytological approach to identifying in vivo targets of the homeotic Ubx, Abd-A and Abd-B proteins. Development 130: 3683–3689.

37. PetrukS, SmithST, SedkovY, MazoA (2008) Association of trxG and PcG proteins with the bxd maintenance element depends on transcriptional activity. Development 135: 2383–2390.

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

39. BrownJL, MucciD, WhiteleyM, DirksenM-L, KassisJA (1998) The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homolgy to the transcription factor YY1. Mol Cell 1: 1057–1064.

40. AtchisonL, GhiasA, WilkinsonF, BoniniN, AtchisonML (2003) Transcription factor YY1 functions as a PcG protein in vivo. EMBO J 22: 1347–1358.

41. MendenhallEM, KocheRP, TruongT, ZhouVW, IssacB, et al. (2010) GC-rich sequence elements recruit PRC2 in mammalian ES cells. PLoS Genet 6: e1001244.

42. VellaP, BarozziI, CuomoA, BonaldiT, PasiniD (2012) Yin Yang 1 extends the Myc-related transcription factors network in embryonic stem cells. Nucleic Acids Res 40: 3403–3418.

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

44. ChambersI, SmithA (2004) Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23: 7150–7160.

45. PetrukS, SedkovY, JohnstonDM, HodgsonJW, BlackKL, et al. (2012) TrxG and PcG proteins but not methylated histones remain associated with DNA through replication. Cell 150: 922–933.

46. AlfieriC, GambettaMC, MatosR, GlattS, SehrP, et al. (2013) Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements. Genes Dev 27: 2367–2379.

47. WangL, JahrenN, MillerEL, KetelCS, MallinDR (2010) Comparative analysis of chromatin binding by Sex Comb on Midleg (SCM) and other polycomb group repressors at a Drosophila Hox gene. Mol Cell Biol 30: 2584–2593.

48. OrsiGA, KasinathanS, HughesKT, Saminadin-PeterS, HenikoffS, et al. (2014) High-resolution mapping defines the cooperative architecture of Polycomb response elements. Genome Res doi:10.1101/gr.163642.113

49. PouxS, MelfiR, PirrottaV (2001) Establishment of Polycomb silencing requires a transient interaction between PC and ESC. Genes Dev 15: 2509–2514.

50. NicolJW, HeltGA, BlanchardSGJr, RajaA, LoraineAE (2009) The Integrated Genome Browser: free software for distribution and exploration of genome-scale datasets. Bioinformatics 25: 2730–2731.

51. FongCY, ChakLL, BiswasA, TanJH, GauthamanK, et al. (2011) Human Wharton's Jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev Rep 7: 1–16.

52. IrizarryRA, BolstadBM, CollinF, CopeLM, HobbsB, et al. (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31: e15.

53. DjebaliS, DavisCA, MerkelA, DobinA, LassmannT, et al. (2012) Landscape of transcription in human cells. Nature 489: 101–108.

54. BaileyTL, BodenM, BuskeFA, FrithM, GrantCE, et al. (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37 (Web Server issue) W202–208.

55. CrooksGE, HonG, ChandoniaJM, BrennerSE (2004) WebLogo: A sequence logo generator. Genome Res 14: 1188–1190.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 7
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#