Modular Insulators Genome Wide Search for Composite CTCFThyroid Hormone Receptor Binding Sites 英文参考文献.docVIP

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Modular Insulators Genome Wide Search for Composite CTCFThyroid Hormone Receptor Binding Sites 英文参考文献.doc

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Modular Insulators Genome Wide Search for Composite CTCFThyroid Hormone Receptor Binding Sites 英文参考文献

ModularInsulators:GenomeWideSearchforComposite CTCF/ThyroidHormoneReceptorBindingSites OliverWeth,ChristineWeth,MarekBartkuhn,JoergLeers,FlorianUhle¤,RainerRenkawitz* InstituteforGenetics,Justus-Liebig-UniversityGiessen,Giessen,Germany Abstract The conserved 11 zinc-finger protein CTCF is involved in several transcriptional mechanisms, including insulation and enhancerblocking.WehadpreviouslyidentifiedtwocompositeelementsconsistingofaCTCFandaTRbindingsiteatthe chickenlysozymeandthehumanc-mycgenes.Usingtheseithasbeendemonstratedthatthyroidhormonemediatesthe reliefofenhancerblockingeventhoughCTCFremainsboundtoitsbindingsite.Herewewishedtodeterminewhether CTCFandTRcombinedsitesarerepresentativeofageneralfeatureofthegenome,andwhethersuchsitesarefunctionalin regulatingenhancerblocking.Genomewideanalysisrevealedthatabout18%oftheCTCFregionsharboredatleastoneof the four different palindromic or repeated sequence arrangements typical for the binding of TR homodimers or TR/RXR heterodimers.Functionalanalysisof10differentcompositeelementsofthyroidhormoneresponsivegeneswasperformed usingepisomalconstructs.TheepisomalsystemallowedrecapitulatingCTCFmediatedenhancerblockingfunctiontobe dependent on poly (ADP)-ribose modification and to mediate histone deacetylation. Furthermore, thyroid hormone sensitive enhancer blocking could be shown for one of these new composite elements. Remarkably, not only did the regulationofenhancerblockingrequirefunctionalTRbinding,butalsothebasalenhancerblockingactivityofCTCFwas dependent on the binding of the unliganded TR. Thus, a number of composite CTCF/TR binding sites may represent a subsetofothermodularCTCFcompositesites,suchasgroupsofmultipleCTCFsitesorofCTCF/Oct4,CTCF/KaisoorCTCF/ Yy1combinations. Citation:WethO,WethC,BartkuhnM,LeersJ,UhleF,etal.(2010)ModularInsulators:GenomeWideSearchforCompositeCTCF/ThyroidHormoneReceptor BindingSites.PLoSONE5(4):e10119.doi:10.1371/journal.pone.0010119 Editor:LaszloTora,InstituteofGeneticsandMolecularandCe