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Papers In Press, published online ahead of print January 22, 2002
Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1732
Corresponding Author: ohank{at}mednet.ucla.edu
Chromatin remodeling is a key step in overcoming the nucleosomal repression of active transcription in eukaryotes. The mammalian SWI/SNF ATP-dependent chromatin-remodeling complexes contain multiple subunits. The ATPase activities in these complexes are attributable to either BRG-1 or the related brahma protein. The aryl hydrocarbon receptor (AHR), after binding xenobiotic ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), associates with the AHR nuclear translocator (ARNT), and the dimer so formed activates transcription of several genes, including the cytochrome P4501A1 (CYP1A1) gene. We show that BRG-1 potentiates AHR/ARNT-mediated reporter gene activity in a TCDD dependent fashion in Hepa1c1c7 cells. Introduction of BRG-1 into the BRG-1 and hBrm deficient SW13 and C33A human cell lines also enhances expression from a transiently transfected AHR/ARNT-dependent reporter gene. Replenishment of BRG-1 to SW13 cells also restores endogenous cytochrome P4501A1 (CYP1A1) gene expression, whereas an ATPase deficient mutant of BRG-1 is unable to do so. Chromatin immunoprecipation analysis demonstrated that BRG-1 associates with the enhancer region of the mouse CYP1A1 gene in vivo in a TCDD- and ARNT-dependent fashion, suggesting the specific recruitment of BRG-1 by AHR/ARNT. Finally we demonstrate that the glutamine-rich subdomain of the transcriptional activation domain of AHR can interact with BRG-1. Together these studies reveal a functional involvement of BRG-1 in activating CYP1A1 gene transcription and implicate the importance of ATP-dependent chromatin remodeling activity on inducible gene expression mediated by AHR/ARNT.
J. Biol. Chem, 10.1074/jbc.M110122200
Submitted on October 22, 2001
Revised on January 18, 2002
Accepted on January 21, 2002
Functional involvement of the BRM/SWI2-related gene 1 protein (BRG-1)in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex
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