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Molecular and Cellular Biology, April 1999, p. 2724-2733, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human SWI-SNF Component BRG1 Represses Transcription of the c-fos Gene

Daniel J. Murphy,1 Stephen Hardy,2 and Daniel A. Engel1,*

Department of Microbiology and Cancer Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908,1 and Cell Genesys, Inc., Foster City, California 944042

Received 16 September 1998/Returned for modification 24 October 1998/Accepted 19 January 1999

Yeast and mammalian SWI-SNF complexes regulate transcription through active modification of chromatin structure. Human SW-13 adenocarcinoma cells lack BRG1 protein, a component of SWI-SNF that has a DNA-dependent ATPase activity essential for SWI-SNF function. Expression of BRG1 in SW-13 cells potentiated transcriptional activation by the glucocorticoid receptor, which is known to require SWI-SNF function. BRG1 also specifically repressed transcription from a transfected c-fos promoter and correspondingly blocked transcriptional activation of the endogenous c-fos gene. Mutation of lysine residue 798 in the DNA-dependent ATPase domain of BRG1 significantly reduced its ability to repress c-fos transcription. Repression by BRG1 required the cyclic AMP response element of the c-fos promoter but not nearby binding sites for Sp1, YY1, or TFII-I. Using human C33A cervical carcinoma cells, which lack BRG1 and also express a nonfunctional Rb protein, transcriptional repression by BRG1 was weak unless wild-type Rb was also supplied. Interestingly, Rb-dependent repression by BRG1 was found to take place through a pathway that is independent of transcription factor E2F.

* Corresponding author. Mailing address: Department of Microbiology, University of Virginia School of Medicine, 1300 Jefferson Park Ave., Charlottesville, VA 22908. Phone: (804) 924-8633. Fax: (804) 982-1071. E-mail: dae2s{at}virginia.edu.

Molecular and Cellular Biology, April 1999, p. 2724-2733, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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