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J. Biol. Chem., Vol. 282, Issue 52, 37429-37435, December 28, 2007

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The Activity of p53 Is Differentially Regulated by Brm- and Brg1-containing SWI/SNF Chromatin Remodeling Complexes^*

Yang Xu¹, Jin Zhang¹, and Xinbin Chen²

From the Center for Comparative Oncology, University of California, Davis, California 95616 and Department of Hematology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China

Brahma (Brm) and Brahma-related gene-1 (Brg1) ATPases share similarities in structure and function, but their presence in human SWI/SNF chromatin remodeling complexes is mutually exclusive. Although Brm and Brg1 can compensate for each other, it is possible that Brm and Brg1 have their unique properties to differentially regulate gene expression in vivo. To explore this, we examined the requirement of Brm and Brg1 for p53-dependent transcription, especially p53-mediated induction of p21 and MDM2, using cell lines in which Brm or Brg1 could be inducibly knocked down. We found that Brg1, but not Brm, is required for p21 induction in MCF7 cells. However, in Brg1-deficient H1299 cells, Brm is also required for p21 induction. Likewise, Brm is necessary for induction of p21 in MCF7 cells in which Brg1 is stably knocked down. In contrast, Brg1 has little, if any, effect on p53-mediated induction of MDM2 in cells that have Brm and vice versa. In addition, we demonstrated that the impaired induction of p21 upon Brg1 knockdown is at least in part due to decreased p53 binding to the p21 promoter. Taken together, we provided evidence that Brg1 is preferentially recruited by p53 for inducing a subset of target genes through chromatin remodeling. Thus, we hypothesize that the potential tumor suppressor function for Brg1 is mediated in part through the p53 pathway.

Received for publication, July 23, 2007 , and in revised form, September 10, 2007.

^* This work was supported in part by National Institutes of Health Grants CA076069, CA081237, and CA102188. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Center for Comparative Oncology, University of California, 2128 Tupper Hall, Davis, CA 95616. Tel.: 530-754-8404; Fax: 530-752-6042; E-mail: xbchen{at}ucdavis.edu.

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