Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: A humoral mechanism to reset a peripheral clock

Peter McNamara, Sang beom Seo, Radu Daniel Rudic, Amita Sehgal, Debabrata Chakravarti, Garret A. FitzGerald

Research output: Contribution to journalArticle

353 Scopus citations

Abstract

Circadian clock genes are expressed in the suprachiasmatic nucleus and in peripheral tissues to regulate cyclically physiological processes. Synchronization of peripheral oscillators is thought to involve humoral signals, but the mechanisms by which these are mediated and integrated are poorly understood. We report a hormone-dependent interaction of the nuclear receptors, RARα and RXRα, with CLOCK and MOP4. These interactions negatively regulate CLOCK/MOP4: BMAL1-mediated transcriptional activation of clock gene expression in vascular cells. MOP4 exhibits a robust rhythm in the vasculature, and retinoic acid can phase shift Per2 mRNA rhythmicity in vivo and in serum-induced smooth muscle cells in vitro, providing a molecular mechanism for hormonal control of clock gene expression. We propose that circadian or periodic availability of nuclear hormones may play a critical role in resetting a peripheral vascular clock.

Original languageEnglish (US)
Pages (from-to)877-889
Number of pages13
JournalCell
Volume105
Issue number7
DOIs
StatePublished - Jun 29 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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