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The Groucho Co-repressor Is Primarily Recruited to Local Target Sites in Active Chromatin to Attenuate Transcription
Repression by transcription factors plays a central role in gene regulation. The Groucho/Transducin-Like Enhancer of split (Gro/TLE) family of co-repressors interacts with many different transcription factors and has many essential roles during animal development. Groucho/TLE proteins form oligomers that are necessary for target gene repression in some contexts. We have profiled the genome-wide recruitment of the founding member of this family, Groucho (from Drosophila) to gain insight into how and where it binds with respect to target genes and to identify factors associated with its binding. We find that Groucho binds in discrete peaks, frequently at transcription start sites, and that blocking Groucho from forming oligomers does not significantly change the pattern of Groucho recruitment. Although Groucho acts as a repressor, Groucho binding is enriched in chromatin that is permissive for transcription, and we find that it acts to attenuate rather than completely silence target gene expression. Thus, Groucho does not act as an “on/off” switch on target gene expression, but rather as a “mute” button.
Vyšlo v časopise: The Groucho Co-repressor Is Primarily Recruited to Local Target Sites in Active Chromatin to Attenuate Transcription. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004595
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004595Souhrn
Repression by transcription factors plays a central role in gene regulation. The Groucho/Transducin-Like Enhancer of split (Gro/TLE) family of co-repressors interacts with many different transcription factors and has many essential roles during animal development. Groucho/TLE proteins form oligomers that are necessary for target gene repression in some contexts. We have profiled the genome-wide recruitment of the founding member of this family, Groucho (from Drosophila) to gain insight into how and where it binds with respect to target genes and to identify factors associated with its binding. We find that Groucho binds in discrete peaks, frequently at transcription start sites, and that blocking Groucho from forming oligomers does not significantly change the pattern of Groucho recruitment. Although Groucho acts as a repressor, Groucho binding is enriched in chromatin that is permissive for transcription, and we find that it acts to attenuate rather than completely silence target gene expression. Thus, Groucho does not act as an “on/off” switch on target gene expression, but rather as a “mute” button.
Zdroje
1. BuscarletM, StifaniS (2007) The ‘Marx’ of Groucho on development and disease. Trends Cell Biol 17 : 353–361.
2. CinnamonE, ParoushZ (2008) Context-dependent regulation of Groucho/TLE-mediated repression. Curr Opin Genet Dev 18 : 435–440.
3. JenningsBH, Ish-HorowiczD (2008) The Groucho/TLE/Grg family of transcriptional co-repressors. Genome Biol 9 : 205.
4. Turki-JudehW, CoureyAJ (2012) Groucho: a corepressor with instructive roles in development. Curr Top Dev Biol 98 : 65–96.
5. ParoushZ, FinleyRLJr, KiddT, WainwrightSM, InghamPW, et al. (1994) Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. Cell 79 : 805–815.
6. ChenG, CoureyAJ (2000) Groucho/TLE family proteins and transcriptional repression. Gene 249 : 1–16.
7. GasperowiczM, OttoF (2005) Mammalian Groucho homologs: redundancy or specificity? J Cell Biochem 95 : 670–687.
8. StifaniS, BlaumuellerCM, RedheadNJ, HillRE, Artavanis-TsakonasS (1992) Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. Nature Genet 2 : 119–127.
9. ChenG, NguyenPH, CoureyAJ (1998) A role for Groucho tetramerization in transcriptional repression. Mol Cell Biol 18 : 7259–7268.
10. PintoM, LobeCG (1996) Products of the grg (Groucho-related gene) family can dimerize through the amino-terminal Q domain. J Biol Chem 271 : 33026–33031.
11. SongH, HassonP, ParoushZ, CoureyAJ (2004) Groucho oligomerization is required for repression in vivo. Mol Cell Biol 24 : 4341–4350.
12. RooseJ, MolenaarM, PetersonJ, HurenkampJ, BrantjesH, et al. (1998) The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395 : 608–612.
13. BrantjesH, RooseJ, van De WeteringM, CleversH (2001) All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res 29 : 1410–1419.
14. PicklesLM, RoeSM, HemingwayEJ, StifaniS, PearlLH (2002) Crystal structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 transcriptional corepressor. Structure 10 : 751–761.
15. JenningsBH, PicklesLM, WainwrightSM, RoeSM, PearlLH, et al. (2006) Molecular recognition of transcriptional repressor motifs by the WD domain of the Groucho/TLE corepressor. Mol Cell 22 : 645–655.
16. PalapartiA, BaratzA, StifaniS (1997) The Groucho/transducin-like enhancer of split transcriptional repressors interact with the genetically defined amino-terminal silencing domain of histone H3. J Biol Chem 272 : 26604–26610.
17. ChenG, FernandezJ, MischeS, CoureyAJ (1999) A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development. Genes Dev 13 : 2218–2230.
18. MartinezCA, ArnostiDN (2008) Spreading of a corepressor linked to action of long-range repressor hairy. Mol Cell Biol 28 : 2792–2802.
19. LiLM, ArnostiDN (2011) Long - and short-range transcriptional repressors induce distinct chromatin states on repressed genes. Curr Biol 21 : 406–412.
20. WinklerCJ, PonceA, CoureyAJ (2010) Groucho-mediated repression may result from a histone deacetylase-dependent increase in nucleosome density. PLoS One 5: e10166.
21. MannervikM, LevineM (1999) The Rpd3 histone deacetylase is required for segmentation of the Drosophila embryo. Proc Natl Acad Sci U S A 96 : 6797–6801.
22. NegreN, BrownCD, MaL, BristowCA, MillerSW, et al. (2011) A cis-regulatory map of the Drosophila genome. Nature 471 : 527–531.
23. FilionGJ, van BemmelJG, BraunschweigU, TalhoutW, KindJ, et al. (2010) Systematic Protein Location Mapping Reveals Five Principal Chromatin Types in Drosophila Cells. Cell 143 : 212–224.
24. CelnikerSE, DillonLA, GersteinMB, GunsalusKC, HenikoffS, et al. (2009) Unlocking the secrets of the genome. Nature 459 : 927–930.
25. SimsD, SudberyI, IlottNE, HegerA, PontingCP (2014) Sequencing depth and coverage: key considerations in genomic analyses. Nat Rev Genet 15 : 121–132.
26. BaroloS, StoneT, BangAG, PosakonyJW (2002) Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless. Genes Dev 16 : 1964–1976.
27. NagelAC, KrejciA, TeninG, Bravo-PatinoA, BrayS, et al. (2005) Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors. Mol Cell Biol 25 : 10433–10441.
28. Terriente-FelixA, LiJ, CollinsS, MulliganA, ReekieI, et al. (2013) Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme. Development 140 : 926–937.
29. GraveleyBR, BrooksAN, CarlsonJW, DuffMO, LandolinJM, et al. (2011) The developmental transcriptome of Drosophila melanogaster. Nature 471 : 473–479.
30. BaileyTL, MachanickP (2012) Inferring direct DNA binding from ChIP-seq. Nucleic Acids Res 40: e128.
31. CherbasL, WillinghamA, ZhangD, YangL, ZouY, et al. (2011) The transcriptional diversity of 25 Drosophila cell lines. Genome Res 21 : 301–314.
32. MohammedH, D'SantosC, SerandourAA, AliHR, BrownGD, et al. (2013) Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor. Cell Rep 3 : 342–349.
33. WheelerJC, VanderZwanC, XuX, SwantekD, TraceyWD, et al. (2002) Distinct in vivo requirements for establishment versus maintenance of transcriptional repression. Nat Genet 32 : 206–210.
34. TieF, BanerjeeR, StrattonCA, Prasad-SinhaJ, StepanikV, et al. (2009) CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136 : 3131–3141.
35. KellnerWA, RamosE, Van BortleK, TakenakaN, CorcesVG (2012) Genome-wide phosphoacetylation of histone H3 at Drosophila enhancers and promoters. Genome Res 22 : 1081–1088.
36. ZentnerGE, HenikoffS (2013) Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20 : 259–266.
37. CockerillPN (2011) Structure and function of active chromatin and DNase I hypersensitive sites. Febs J 278 : 2182–2210.
38. CoureyAJ, JiaS (2001) Transcriptional repression: the long and the short of it. Genes Dev 15 : 2786–2796.
39. LiJ, GilmourDS (2011) Promoter proximal pausing and the control of gene expression. Curr Opin Genet Dev 21 : 231–235.
40. LevineM (2011) Paused RNA polymerase II as a developmental checkpoint. Cell 145 : 502–511.
41. AdelmanK, LisJT (2012) Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat Rev Genet 13 : 720–731.
42. JenningsBH (2013) Pausing for thought: disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis. Bioessays 35 : 553–560.
43. LaghaM, BothmaJP, EspositoE, NgS, StefanikL, et al. (2013) Paused Pol II coordinates tissue morphogenesis in the Drosophila embryo. Cell 153 : 976–987.
44. SaundersA, CoreLJ, SutcliffeC, LisJT, AsheHL (2013) Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription. Genes Dev 27 : 1146–1158.
45. LeeC, LiX, HechmerA, EisenM, BigginMD, et al. (2008) NELF and GAGA factor are linked to promoter-proximal pausing at many genes in Drosophila. Mol Cell Biol 28 : 3290–3300.
46. LiJ, GilmourDS (2013) Distinct mechanisms of transcriptional pausing orchestrated by GAGA factor and M1BP, a novel transcription factor. The EMBO J 32 : 1829–1841.
47. BaroloS, LevineM (1997) hairy mediates dominant repression in the Drosophila embryo. EMBO J 16 : 2883–2891.
48. Bianchi-FriasD, OrianA, DelrowJJ, VazquezJ, Rosales-NievesAE, et al. (2004) Hairy transcriptional repression targets and cofactor recruitment in Drosophila. PLoS Biol 2: E178.
49. StraubT, ZabelA, GilfillanGD, FellerC, BeckerPB (2013) Different chromatin interfaces of the Drosophila dosage compensation complex revealed by high-shear ChIP-seq. Genome Res 23 : 473–485.
50. KulaevaOI, NizovtsevaEV, PolikanovYS, UlianovSV, StuditskyVM (2012) Distant activation of transcription: mechanisms of enhancer action. Mol Cell Biol 32 : 4892–4897.
51. StadhoudersR, van den HeuvelA, KolovosP, JornaR, LeslieK, et al. (2012) Transcription regulation by distal enhancers: who's in the loop? Transcription 3 : 181–186.
52. WebberJL, ZhangJ, Mitchell-DickA, RebayI (2013) 3D chromatin interactions organize Yan chromatin occupancy and repression at the even-skipped locus. Genes Dev 27 : 2293–2298.
53. BeumerKJ, CarrollD (2014) Targeted genome engineering techniques in Drosophila. Methods 68 : 29–37.
54. ChanutF, LukA, HeberleinU (2000) A screen for dominant modifiers of ro(Dom), a mutation that disrupts morphogenetic furrow progression in Drosophila, identifies groucho and hairless as regulators of atonal expression. Genetics 156 : 1203–1217.
55. JenningsBH, WainwrightSM, Ish-HorowiczD (2008) Differential in vivo requirements for oligomerization during Groucho-mediated repression. EMBO Rep 9 : 76–83.
56. GilchristDA, FrommG, Dos SantosG, PhamLN, McDanielIE, et al. (2012) Regulating the regulators: the pervasive effects of Pol II pausing on stimulus-responsive gene networks. Genes Dev 26 : 933–944.
57. JenningsBH, ShahS, YamaguchiY, SekiM, PhillipsRG, et al. (2004) Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila. Curr Biol 14 : 1680–1684.
58. DoeCQ (1992) Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system. Development 116 : 855–863.
59. JenningsB, PreissA, DelidakisC, BrayS (1994) The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo. Development 120 : 3537–3548.
60. HousdenBE, FuAQ, KrejciA, BernardF, FischerB, et al. (2013) Transcriptional Dynamics Elicited by a Short Pulse of Notch Activation Involves Feed-Forward Regulation by E(spl)/Hes Genes. PLoS Genet 9: e1003162.
61. ReynoldsN, O'ShaughnessyA, HendrichB (2013) Transcriptional repressors: multifaceted regulators of gene expression. Development 140 : 505–512.
62. LandtSG, MarinovGK, KundajeA, KheradpourP, PauliF, et al. (2012) ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res 22 : 1813–1831.
63. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.
64. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25 : 2078–2079.
65. ZhangY, LiuT, MeyerCA, EeckhouteJ, JohnsonDS, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9: R137.
66. ZhuLJ, GazinC, LawsonND, PagesH, LinSM, et al. (2010) ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data. BMC Bioinformatics 11 : 237.
67. Huang daW, ShermanBT, LempickiRA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 : 44–57.
68. RobinsonMD, McCarthyDJ, SmythGK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 : 139–140.
69. BergmanCM, CarlsonJW, CelnikerSE (2005) Drosophila DNase I footprint database: a systematic genome annotation of transcription factor binding sites in the fruitfly, Drosophila melanogaster. Bioinformatics 21 : 1747–1749.
70. KulakovskiyIV, MakeevVJ (2009) Discovery of DNA motifs recognized by transcription factors through integration of different experimental sources. Biophysics 54 : 667–674.
71. EnuamehMS, AsriyanY, RichardsA, ChristensenRG, HallVL, et al. (2013) Global analysis of Drosophila Cys(2)-His(2) zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. Genome Res 23 : 928–940.
72. HeinzS, BennerC, SpannN, BertolinoE, LinYC, et al. (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38 : 576–589.
73. TrapnellC, PachterL, SalzbergSL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25 : 1105–1111.
74. BenjaminiY, HochbergY (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57 : 289–300.
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