Cross-talk between hypoxic and circadian pathways: cooperative roles for hypoxia-inducible factor 1α and CLOCK in transcriptional activation of the vasopressin gene

MBT Ghorbel, JM Coulson, D Murphy

Research output: Contribution to journalArticle (Academic Journal)peer-review

42 Citations (Scopus)

Abstract

The vasopressin gene is expressed in the suprachiasmatic nucleus where the basic helix-loop-helix (bHLH)-PAS factors CLOCK and MOP3 regulate circadian expression through interactions with E-box sequences. We have examined vasopressin gene regulation by HIF-1[alpha], a bHLH-PAS factor involved in responses to hypoxia. By transfecting Neuro-2A cells with 5' flanking regions of vasopressin gene driving a luciferase reporter, we have shown that CLOCK and HIF-1[alpha] cooperate in the induction of expression from 1000 bp and 350 bp of the vasopressin promoter but do not activate a 120-bp promoter fragment. The region between -191 and -128 contains an E-box A that appears to be essential for HIF-1[alpha]/CLOCK-mediated transcriptional activity. However, gel-shift analysis shows that the cooperative effect of HIF-1[alpha] and CLOCK results in MOP3 binding, but does not involve heterodimerization of HIF-1[alpha]/CLOCK, at E-box A. These data indicate that cross-talk between mediators of hypoxic and circadian pathways can regulate target genes.
Translated title of the contributionCross-talk between hypoxic and circadian pathways: cooperative roles for hypoxia-inducible factor 1α and CLOCK in transcriptional activation of the vasopressin gene
Original languageEnglish
Pages (from-to)396 - 404
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume22 (3)
DOIs
Publication statusPublished - Mar 2003

Bibliographical note

Publisher: Elsevier

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