Heme oxygenase-1 gene enhancer manifests silencing activity in a chromatin environment prior to oxidative stress

Yoshihiro Dohi, Jawed Alam, Masao Yoshizumi, Jiying Sun, Kazuhiko Igarashi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The expression of heme oxygenase-1 (HO-1) is regulated by E1 and E2 enhancers, both of which contain multiple Maf recognition elements (MAREs). In living cells, MAREs are bound by Bach1/MafK heterodimers, hence maintaining a quiescent state of the HO-1 gene (hmox-1). However, in transient transfection assays, they act as transcriptional enhancers. Therefore MAREs may manifest their function only in a chromatin environment. By using NIH3T3 cell pools stably transfected with EGFP reporter genes driven by the wild-type or mutated E2 enhancer, we demonstrate that the E2 MAREs function as transcriptional silencers depending on the binding of Bach1/MafK heterodimer in vivo only in a chromatin environment. After cadmium treatment, they switched into transcriptional enhancers. Surprisingly, single MARE site did not exhibit such function. Furthermore, by using DNase I hypersensitivity assay, we demonstrate that simple chromatin condensations were not involved in the Bach1-mediated repression. We conclude that, in a chromatin environment, the E2 MAREs function as transcriptional silencers depending on binding of Bach1/MafK heterodimer.

Original languageEnglish
Pages (from-to)60-67
Number of pages8
JournalAntioxidants and Redox Signaling
Volume8
Issue number1-2
DOIs
Publication statusPublished - 2006 Jan 1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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