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Molecular and Cellular Biology, February 2000, p. 1134-1139, Vol. 20, No. 4
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Requirement for TAFII250 Acetyltransferase Activity in Cell Cycle Progression

Elizabeth L. Dunphy, Theron Johnson, Scott S. Auerbach, and Edith H. Wang*

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.

* 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.

Molecular and Cellular Biology, February 2000, p. 1134-1139, Vol. 20, No. 4
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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