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PMID: 16923960 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

BRG1 interacts with Nrf2 to selectively mediate HO-1 induction in response to oxidative stress.

Molecular and cellular biology ·Vol. 26 ·No. 21 ·2006-11-00 ·Pages 7942-52

Zhang J, Ohta T, Maruyama A, Hosoya T, Nishikawa K, Maher JM, Shibahara S, Itoh K, Yamamoto M

Abstract

NF-E2-related factor 2 (Nrf2) regulates antioxidant-responsive element-mediated induction of cytoprotective genes in response to oxidative stress. The purpose of this study was to determine the role of BRG1, a catalytic subunit of SWI2/SNF2-like chromatin-remodeling complexes, in Nrf2-mediated gene expression. Small interfering RNA knockdown of BRG1 in SW480 cells selectively decreased inducible expression of the heme oxygenase 1 (HO-1) gene after diethylmaleate treatment but did not affect other Nrf2 target genes, such as the gene encoding NADPH:quinone oxidoreductase 1 (NQO1). Chromatin immunoprecipitation analysis revealed that Nrf2 recruits BRG1 to both HO-1 and NQO1 regulatory regions. However, BRG1 knockdown selectively decreased the recruitment of RNA polymerase II to the HO-1 promoter but not to the NQO1 promoter. HO-1, but not other Nrf2-regulated genes, harbors a sequence of TG repeats capable of forming Z-DNA with BRG1 assistance. Similarly, replacement of the TG repeats with an alternative Z-DNA-forming sequence led to BRG1-mediated activation of HO-1. These results thus demonstrate that BRG1, through the facilitation of Z-DNA formation and subsequent recruitment of RNA polymerase II, is critical in Nrf2-mediated inducible expression of HO-1.

MeSH Terms
Animals Cell Line Chromatin/metabolism DNA Helicases/genetics,metabolism DNA, Z-Form/metabolism Gene Expression Regulation Heme Oxygenase-1/genetics,metabolism Humans NAD(P)H Dehydrogenase (Quinone)/genetics,metabolism NF-E2-Related Factor 2/genetics,metabolism Nuclear Proteins/genetics,metabolism Oxidative Stress Promoter Regions, Genetic Protein Binding Protein Subunits/genetics,metabolism RNA Polymerase II/metabolism RNA, Small Interfering/metabolism Response Elements Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
Chromatin DNA, Z-Form NF-E2-Related Factor 2 NFE2L2 protein, human Nuclear Proteins Protein Subunits RNA, Small Interfering Transcription Factors HMOX1 protein, human Heme Oxygenase-1 NAD(P)H Dehydrogenase (Quinone) NQO1 protein, human RNA Polymerase II SMARCA4 protein, human DNA Helicases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhang Jianyong
Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8577, Japan.
Ohta Tsutomu
Maruyama Atsushi
Hosoya Tomonori
Nishikawa Keizo
Maher Jonathan M
Shibahara Shigeki
Itoh Ken
Yamamoto Masayuki
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2006-11-00
Epub
2006-00-21
Pages
7942-52
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1636732
Subset
IM
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