Functional involvement of the Brahma/SWI2-related gene 1 protein in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex.
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 immunoprecipitation 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.
Wang
Song
S
Department of Pathology and Laboratory Medicine, Center for the Health Sciences, University of California, Los Angeles, California 90095-1732, USA.
Hankinson
Oliver
O
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004265:DNA Helicases; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D002843:Chromatin; D008024:Ligands; D009687:Nuclear Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases