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

347 Citations (Scopus)

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

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Cytoplasmic and Nuclear Receptors
Blood Vessels
Clocks
Hormones
Physiological Phenomena
Gene Expression
Circadian Clocks
Suprachiasmatic Nucleus
Periodicity
Tretinoin
Gene expression
Transcriptional Activation
Smooth Muscle Myocytes
Messenger RNA
Serum
Phase shift
Genes
Muscle
Synchronization
Chemical activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature : A humoral mechanism to reset a peripheral clock. / McNamara, Peter; Seo, Sang beom; Rudic, Radu Daniel; Sehgal, Amita; Chakravarti, Debabrata; FitzGerald, Garret A.

In: Cell, Vol. 105, No. 7, 29.06.2001, p. 877-889.

Research output: Contribution to journalArticle

McNamara, Peter ; Seo, Sang beom ; Rudic, Radu Daniel ; Sehgal, Amita ; Chakravarti, Debabrata ; FitzGerald, Garret A. / Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature : A humoral mechanism to reset a peripheral clock. In: Cell. 2001 ; Vol. 105, No. 7. pp. 877-889.
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