Requirement for TAF(II)250 acetyltransferase activity in cell cycle progression

The TATA-binding protein (TBP)-associated factor TAF(II)250 is the largest component of the basal transcription factor IID (TFIID). A missense mutatio n that maps to the acetyltransferase domain of TAF(II)250 induces the tempe rature-sensitive (ts) mutant hamster cell lines ts13 and tsBN462 to arrest in late G(1). At the nonpermissive temperature (39.5 degrees C), transcript ion from only a subset of protein encoding genes, including the G(1) cyclin s, is dramatically reduced in the mutant cells. Here we demonstrate that th e ability of the ts13 allele of TAF(II)250 to acetylate histones in vitro i s temperature sensitive suggesting that this enzymatic activity is compromi sed at 39.5 degrees C in the mutant cells. Mutagenesis of a putative acetyl coenzyme A binding site produced a TAF(II)250 protein that displayed signi ficantly reduced histone acetyltransferase activity but retained TBP and TA F(II)150 binding. Expression of this mutant in ts13 cells was unable to com plement the cell cycle arrest or transcriptional defect observed at 39.5 de grees C. These data suggest that TAF(II)250 acetyltransferase activity is r equired for cell cycle progression and regulates the expression of essentia l proliferative control genes.