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M405438200v1
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Papers In Press, published online ahead of print August 17, 2004
J. Biol. Chem, 10.1074/jbc.M405438200
Submitted on May 17, 2004
Revised on August 17, 2004
Accepted on August 17, 2004

Brg-1 is required for maximal transcription of the human MMP-2 gene

Zhendong Ma, Mi Jung Chang, Reesha Shah, Jill Adamski, Xueyan Zhao, and Etty N. Benveniste

Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294

Corresponding Author: Tika{at}uab.edu

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases whose aberrant expression are correlated with tumor invasion and angiogenesis. The transcription factors Sp1, Sp3 and AP-2 are required for constitutive expression of MMP-2 in tumor cells, however, the regulatory mechanisms of MMP-2 expression are not well understood. We investigated the involvement of Brg-1, the ATPase subunit of the SWI/SNF complex, in human MMP-2 gene transcription. Reconstitution of Brg-1 enhances MMP-2 transcription in Brg-1 deficient SW-13 cells. Chromatin immunoprecipitation assay demonstrates that Brg-1 is required for recruitment of Sp1, AP-2 and Pol II to the MMP-2 promoter, while the binding of Sp3 to the MMP-2 promoter is decreased upon Brg-1 reconstitution. Furthermore, Sp1 interacts with Brg-1 in vivo. Restriction enzyme accessibility assays indicate that accessibility of the MMP-2 promoter region is not changed in the absence or presence of Brg-1. These results illustrate the connection between the SWI/SNF complex and optimal expression of MMP-2, and highlight the critical function of Brg-1 in regulating the recruitment of Sp1, Sp3, AP-2 and Pol II to the MMP-2 promoter.


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