Regulatory role of transcription factors TAF1 and TAF7 in cyclin gene expression

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Regulatory role of transcription factors TAF1 and TAF7 in cyclin gene expression

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dc.contributor.advisor Wang, Edith H en_US
dc.contributor.author Kloet, Susan en_US
dc.date.accessioned 2012-09-13T17:34:52Z
dc.date.issued 2012-09-13
dc.date.submitted 2012 en_US
dc.identifier.other Kloet_washington_0250E_10634.pdf en_US
dc.identifier.uri http://hdl.handle.net/1773/20777
dc.description Thesis (Ph.D.)--University of Washington, 2012 en_US
dc.description.abstract The 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.mimetype application/pdf en_US
dc.language.iso en_US en_US
dc.subject en_US
dc.subject.other Molecular biology en_US
dc.subject.other Molecular and cellular biology en_US
dc.title Regulatory role of transcription factors TAF1 and TAF7 in cyclin gene expression en_US
dc.type Thesis en_US
dc.embargo.terms Restrict to UW for 2 years -- then make Open Access en_US
dc.embargo.lift 2014-09-03T17:34:52Z


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