Human SWI-SNF component BRG1 represses transcription of the c-fos gene

Murphy, D.J. , Hardy, S. and Engel, D.A. (1999) Human SWI-SNF component BRG1 represses transcription of the c-fos gene. Molecular and Cellular Biology, 19(4), pp. 2724-33.

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel
Authors: Murphy, D.J., Hardy, S., and Engel, D.A.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Molecular and Cellular Biology
ISSN (Online):1098-5549

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