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

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 activ ity essential for SWI-SNF function. Expression of BRG1 in SW-13 cells poten tiated transcriptional activation by the glucocorticoid receptor, which is known to require SWI-SNF function. BRG1 also specifically repressed transcr iption from a transfected c-fos promoter and correspondingly blocked transc riptional activation of the endogenous c-fos gene. Mutation of lysine resid ue 798 in the DNA-dependent. ATPase domain of BRG1 significantly reduced it s ability to repress c-fos transcription. Repression by BRG1 required the c yclic AMP response element of the c-fos promoter but not nearby binding sit es for Sp1, YY1, or TFII-I. Using human C33A cervical carcinoma cells, whic h lack BRG1 and also express a nonfunctional Rb protein, transcriptional re pression by BRG1 was weak unless wild-type Rb was also supplied, Interestin gly, Rb-dependent repression by BRG1 was found to take place through a path way that is independent of transcription factor E2F.