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dc.contributor.advisorWang, Edith Hen_US
dc.contributor.authorKloet, Susanen_US
dc.date.accessioned2012-09-13T17:34:52Z
dc.date.available2015-12-14T17:55:55Z
dc.date.issued2012-09-13
dc.date.submitted2012en_US
dc.identifier.otherKloet_washington_0250E_10634.pdfen_US
dc.identifier.urihttp://hdl.handle.net/1773/20777
dc.descriptionThesis (Ph.D.)--University of Washington, 2012en_US
dc.description.abstractThe largest transcription factor IID (TFIID) subunit, TBP associated factor 1 (TAF1) possesses protein kinase and histone acetyltransferase (HAT) activities. Both enzymatic activities are essential for transcription from a subset of genes and G1 progression in mammalian cells. TAF7, another TFIID subunit, binds TAF1 and inhibits TAF1 HAT activity. Here we present data demonstrating that disruption of the TAF1/TAF7 interaction within TFIID by protein phosphorylation leads to activation of TAF1 HAT activity and stimulation of cyclin D1 and cyclin A transcription. Overexpression and siRNA knockdown experiments confirmed that TAF7 functions as a transcriptional repressor at these promoters. Release of TAF7 from TFIID by TAF1 phosphorylation of TAF7 increased TAF1 HAT activity and elevated histone H3 acetylation levels at the cyclin D1 and cyclin A promoters. Serine-264 of TAF7 was identified as a substrate for TAF1 kinase activity. Using TAF7 S264A and S264D phospho-mutants, we determined that the phosphorylation state of TAF7 at S264 influences the levels of cyclin D1 and cyclin A transcription and promoter histone H3 acetylation. These studies have uncovered a novel function for the TFIID subunit TAF7 as a phosphorylation-dependent regulator of TAF1-catalyzed histone H3 acetylation at the cyclin D1 and cyclin A promoters.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.rightsCopyright is held by the individual authors.en_US
dc.subjecten_US
dc.subject.otherMolecular biologyen_US
dc.subject.otherMolecular and cellular biologyen_US
dc.titleRegulatory role of transcription factors TAF1 and TAF7 in cyclin gene expressionen_US
dc.typeThesisen_US
dc.embargo.termsRestrict to UW for 2 years -- then make Open Accessen_US


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