#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Preferential Genome Targeting of the CBP Co-Activator by Rel and Smad Proteins in Early Embryos


CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors. Whether CBP/p300 occupies the genome equally with all factors or preferentially binds together with some factors is not known. We therefore compared Drosophila melanogaster CBP (nejire) ChIP–seq peaks with regions bound by 40 different transcription factors in early embryos, and we found high co-occupancy with the Rel-family protein Dorsal. Dorsal is required for CBP occupancy in the embryo, but only at regions where few other factors are present. CBP peaks in mutant embryos lacking nuclear Dorsal are best correlated with TGF-ß/Dpp-signaling and Smad-protein binding. Differences in CBP occupancy in mutant embryos reflect gene expression changes genome-wide, but CBP also occupies some non-expressed genes. The presence of CBP at silent genes does not result in histone acetylation. We find that Polycomb-repressed H3K27me3 chromatin does not preclude CBP binding, but restricts histone acetylation at CBP-bound genomic sites. We conclude that CBP occupancy in Drosophila embryos preferentially overlaps factors controlling dorso-ventral patterning and that CBP binds silent genes without causing histone hyperacetylation.


Vyšlo v časopise: Preferential Genome Targeting of the CBP Co-Activator by Rel and Smad Proteins in Early Embryos. PLoS Genet 8(6): e32767. doi:10.1371/journal.pgen.1002769
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002769

Souhrn

CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors. Whether CBP/p300 occupies the genome equally with all factors or preferentially binds together with some factors is not known. We therefore compared Drosophila melanogaster CBP (nejire) ChIP–seq peaks with regions bound by 40 different transcription factors in early embryos, and we found high co-occupancy with the Rel-family protein Dorsal. Dorsal is required for CBP occupancy in the embryo, but only at regions where few other factors are present. CBP peaks in mutant embryos lacking nuclear Dorsal are best correlated with TGF-ß/Dpp-signaling and Smad-protein binding. Differences in CBP occupancy in mutant embryos reflect gene expression changes genome-wide, but CBP also occupies some non-expressed genes. The presence of CBP at silent genes does not result in histone acetylation. We find that Polycomb-repressed H3K27me3 chromatin does not preclude CBP binding, but restricts histone acetylation at CBP-bound genomic sites. We conclude that CBP occupancy in Drosophila embryos preferentially overlaps factors controlling dorso-ventral patterning and that CBP binds silent genes without causing histone hyperacetylation.


Zdroje

1. BedfordDCKasperLHFukuyamaTBrindlePK 2010 Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases. Epigenetics 5 9 15

2. HeintzmanNDHonGCHawkinsRDKheradpourPStarkA 2009 Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459 108 112

3. ViselABlowMJLiZZhangTAkiyamaJA 2009 ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457 854 858

4. AkimaruHChenYDaiPHouDXNonakaM 1997 Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling. Nature 386 735 738

5. NegreNBrownCDMaLBristowCAMillerSW 2011 A cis-regulatory map of the Drosophila genome. Nature 471 527 531

6. GoodmanRHSmolikS 2000 CBP/p300 in cell growth, transformation, and development. Genes & Development 14 1553 1577

7. AkimaruHHouDXIshiiS 1997 Drosophila CBP is required for dorsal-dependent twist gene expression. Nat Genet 17 211 214

8. AsheHLMannervikMLevineM 2000 Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo. Development 127 3305 3312

9. LiljaTAiharaHStabellMNibuYMannervikM 2007 The acetyltransferase activity of Drosophila CBP is dispensable for regulation of the Dpp pathway in the early embryo. Dev Biol 305 650 658

10. LiljaTQiDStabellMMannervikM 2003 The CBP coactivator functions both upstream and downstream of Dpp/Screw signaling in the early Drosophila embryo. Dev Biol 262 294 302

11. WaltzerLBienzM 1999 A function of CBP as a transcriptional co-activator during Dpp signalling. EMBO J 18 1630 1641

12. HongJWHendrixDAPapatsenkoDLevineMS 2008 How the Dorsal gradient works: insights from postgenome technologies. Proc Natl Acad Sci U S A 105 20072 20076

13. MorisatoDAndersonKV 1994 The spatzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. Cell 76 677 688

14. MoussianBRothS 2005 Dorsoventral axis formation in the Drosophila embryo–shaping and transducing a morphogen gradient. Current biology 15 R887 899

15. SchneiderDSHudsonKLLinTYAndersonKV 1991 Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo. Genes & Development 5 797 807

16. ReevesGTStathopoulosA 2009 Graded dorsal and differential gene regulation in the Drosophila embryo. Cold Spring Harbor perspectives in biology 1 a000836

17. JiangJCaiHZhouQLevineM 1993 Conversion of a dorsal-dependent silencer into an enhancer: evidence for dorsal corepressors. EMBO J 12 3201 3209

18. KirovNZhelninLShahJRushlowC 1993 Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila. EMBO J 12 3193 3199

19. DubnicoffTValentineSAChenGShiTLengyelJA 1997 Conversion of dorsal from an activator to a repressor by the global corepressor Groucho. Genes & Development 11 2952 2957

20. AffolterMMartyTViganoMAJazwinskaA 2001 Nuclear interpretation of Dpp signaling in Drosophila. EMBO J 20 3298 3305

21. MacArthurSLiXYLiJBrownJBChuHC 2009 Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol 10 R80

22. RoySErnstJKharchenkoPVKheradpourPNegreN 2010 Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330 1787 1797

23. BigginMD 2011 Animal transcription networks as highly connected, quantitative continua. Developmental Cell 21 611 626

24. PhochanukulNRussellS 2010 No backbone but lots of Sox: Invertebrate Sox genes. The International Journal of Biochemistry & Cell Biology 42 453 464

25. StathopoulosAVan DrenthMErivesAMarksteinMLevineM 2002 Whole-genome analysis of dorsal-ventral patterning in the Drosophila embryo. Cell 111 687 701

26. FuDMaJ 2005 Interplay between positive and negative activities that influence the role of Bicoid in transcription. Nucleic Acids Research 33 3985 3993

27. FuDWenYMaJ 2004 The co-activator CREB-binding protein participates in enhancer-dependent activities of bicoid. The Journal of Biological Chemistry 279 48725 48733

28. HeFSaundersTEWenYCheungDJiaoR 2010 Shaping a morphogen gradient for positional precision. Biophysical Journal 99 697 707

29. LiangHLNienCYLiuHYMetzsteinMMKirovN 2008 The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila. Nature 456 400 403

30. NienCYLiangHLButcherSSunYFuS 2011 Temporal coordination of gene networks by Zelda in the early Drosophila embryo. PLoS Genet 7 e1002339 doi:10.1371/journal.pgen.1002339

31. HarrisonMMLiXYKaplanTBotchanMREisenMB 2011 Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition. PLoS Genet 7 e1002266 doi:10.1371/journal.pgen.1002266

32. WongKHStruhlK 2011 The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein. Genes & Development 25 2525 2539

33. ChenGFernandezJMischeSCoureyAJ 1999 A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development. Genes & Development 13 2218 2230

34. BellOSchwaigerMOakeleyEJLienertFBeiselC 2010 Accessibility of the Drosophila genome discriminates PcG repression, H4K16 acetylation and replication timing. Nature Structural & Molecular Biology 17 894 900

35. SimonJAKingstonRE 2009 Mechanisms of polycomb gene silencing: knowns and unknowns. Nature Reviews Molecular Cell Biology 10 697 708

36. YangZYikJHChenRHeNJangMK 2005 Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Molecular Cell 19 535 545

37. JinQYuLRWangLZhangZKasperLH 2011 Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J 30 249 262

38. TieFBanerjeeRStrattonCAPrasad-SinhaJStepanikV 2009 CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136 3131 3141

39. DasCLuciaMSHansenKCTylerJK 2009 CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459 113 117

40. OngCTCorcesVG 2011 Enhancer function: new insights into the regulation of tissue-specific gene expression. Nature Reviews Genetics 12 283 293

41. PapatsenkoDGoltsevYLevineM 2009 Organization of developmental enhancers in the Drosophila embryo. Nucleic Acids Research 37 5665 5677

42. KrebsARKarmodiyaKLindahl-AllenMStruhlKToraL 2011 SAGA and ATAC histone acetyl transferase complexes regulate distinct sets of genes and ATAC defines a class of p300-independent enhancers. Molecular Cell 44 410 423

43. JiangJHoeyTLevineM 1991 Autoregulation of a segmentation gene in Drosophila: combinatorial interaction of the even-skipped homeo box protein with a distal enhancer element. Genes & Development 5 265 277

44. TautzDPfeifleC 1989 A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma 98 81 85

45. QiDJinHLiljaTMannervikM 2006 Drosophila Reptin and other TIP60 complex components promote generation of silent chromatin. Genetics 174 241 251

46. GraveleyBRBrooksANCarlsonJWDuffMOLandolinJM 2011 The developmental transcriptome of Drosophila melanogaster. Nature 471 473 479

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2012 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

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#