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Molecular and Cellular Biology, February 2000, p. 1134-1139, Vol. 20, No. 4
Department of Pharmacology, School of
Medicine, University of Washington, Seattle, Washington 98195-7280
Received 28 September 1999/Returned for modification 27 October
1999/Accepted 15 November 1999
The TATA-binding protein (TBP)-associated factor
TAFII250 is the largest component of the basal
transcription factor IID (TFIID). A missense mutation that maps to the
acetyltransferase domain of TAFII250 induces the
temperature-sensitive (ts) mutant hamster cell lines ts13
and tsBN462 to arrest in late G1. At the nonpermissive temperature (39.5°C), transcription from only a subset of protein encoding genes, including the G1 cyclins, is dramatically
reduced in the mutant cells. Here we demonstrate that the ability of
the ts13 allele of TAFII250 to acetylate
histones in vitro is temperature sensitive suggesting that this
enzymatic activity is compromised at 39.5°C in the mutant cells.
Mutagenesis of a putative acetyl coenzyme A binding site produced a
TAFII250 protein that displayed significantly reduced
histone acetyltransferase activity but retained TBP and
TAFII150 binding. Expression of this mutant in ts13 cells was unable to complement the cell cycle arrest or transcriptional defect observed at 39.5°C. These data suggest that
TAFII250 acetyltransferase activity is required for cell
cycle progression and regulates the expression of essential
proliferative control genes.
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Copyright © 2000, American Society for Microbiology. All rights reserved.
Requirement for TAFII250
Acetyltransferase Activity in Cell Cycle Progression
*
Corresponding author. Mailing address: Department of
Pharmacology, School of Medicine, University of Washington, Seattle, WA
98195-7280. Phone: (206) 616-5376. Fax: (206) 685-3822. E-mail: ehwang{at}u.washington.edu.
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