A central mechanism in cellular defence against oxidative or electrophilic stress is mediated by transcriptional induction of genes via the ARE (antioxidant-response element), a cis-acting sequence present in the regulatory regions of genes involved in the detoxification and elimination of reactive oxidants and electrophiles. The ARE binds different bZIP (basic-region leucine zipper) transcription factors, most notably Nrf2 (nuclear factor-erythroid 2-related factor 2) that functions as a transcriptional activator via heterodimerization with small Maf proteins. Although ARE activation by Nrf2 is relatively well understood, the mechanisms by which ARE-mediated signalling is down-regulated are poorly known. Transcription factor BACH1 [BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1] binds to ARE-like sequences, functioning as a transcriptional repressor in a subset of ARE-regulated genes, thus antagonizing the activator function of Nrf2. In the present study, we have demonstrated that BACH1 itself is regulated by Nrf2 as it is induced by Nrf2 overexpression and by Nrf2-activating agents in an Nrf2-dependent manner. Furthermore, a functional ARE site was identified at +1411 from the transcription start site of transcript variant 2 of BACH1. We conclude that BACH1 is a bona fide Nrf2 target gene and that induction of BACH1 by Nrf2 may serve as a feedback-inhibitory mechanism for ARE-mediated gene regulation.
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Research Article|
November 14 2011
Novel insights into the regulation of antioxidant-response-elementmediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2
Henna-Kaisa Jyrkkänen;
Henna-Kaisa Jyrkkänen
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Suvi Kuosmanen;
Suvi Kuosmanen
†Department of Biosciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Merja Heinäniemi;
Merja Heinäniemi
‡Life Sciences Research Unit, University of Luxembourg, L-1511, Luxembourg, Luxembourg
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Heidi Laitinen;
Heidi Laitinen
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Emilia Kansanen;
Emilia Kansanen
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Eero Mella-Aho;
Eero Mella-Aho
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Hanna Leinonen;
Hanna Leinonen
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Seppo Ylä-Herttuala;
Seppo Ylä-Herttuala
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
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Anna-Liisa Levonen
Anna-Liisa Levonen
1
*Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FIN-70211, Kuopio, Finland
1To whom correspondence should be addressed (email anna-liisa.levonen@uef.fi).
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Publisher: Portland Press Ltd
Received:
March 23 2011
Revision Received:
August 03 2011
Accepted:
August 03 2011
Accepted Manuscript online:
August 03 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 440 (2): 167–174.
Article history
Received:
March 23 2011
Revision Received:
August 03 2011
Accepted:
August 03 2011
Accepted Manuscript online:
August 03 2011
Citation
Henna-Kaisa Jyrkkänen, Suvi Kuosmanen, Merja Heinäniemi, Heidi Laitinen, Emilia Kansanen, Eero Mella-Aho, Hanna Leinonen, Seppo Ylä-Herttuala, Anna-Liisa Levonen; Novel insights into the regulation of antioxidant-response-elementmediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2. Biochem J 1 December 2011; 440 (2): 167–174. doi: https://doi.org/10.1042/BJ20110526
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