Brg-1 is required for maximal transcription of the human matrix metalloproteinase-2 gene.
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 polymerase II to the MMP-2 promoter, whereas 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 polymerase II to the MMP-2 promoter.
Ma
Zhendong
Z
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Chang
Mi Jung
MJ
Shah
Reesha
R
Adamski
Jill
J
Zhao
Xueyan
X
Benveniste
Etty N
EN
D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D020778:Matrix Metalloproteinase 2; C084108:SMARCA4 protein, human; D004265:DNA Helicases