Phosphorylation-dependent regulation of cyclin D1 and cyclin A gene transcription by TFIID subunits TAF1 and TAF7.
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 G(1) 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 gene transcription. Overexpression and small interfering RNA 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 phosphomutants, we determined that the phosphorylation state of TAF7 at S264 influences the levels of cyclin D1 and cyclin A gene transcription and promoter histone H3 acetylation. Our 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.
Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, USA.
Susan L
SL
Kloet
Jennifer L
JL
Whiting
Phil
P
Gafken
Jeff
J
Ranish
Edith H
EH
Wang
D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D007313:Insecta / Q000166:cytology; D010766:Phosphorylation; D025941:Protein Interaction Mapping / Q000379:methods; D012694:Serine / Q000737:chemistry; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
D019925:Cyclin A; D006657:Histones; C091537:TAF7 protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D019938:Cyclin D1; D012694:Serine; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa