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

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, ...
RAR alpha and RXR alpha, 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.
Mesh Terms:
3T3 Cells, Animals, Basic Helix-Loop-Helix Transcription Factors, Biological Clocks, Blood Vessels, CLOCK Proteins, Cell Cycle Proteins, Circadian Rhythm, Dexamethasone, Genes, Reporter, Glucocorticoids, Humans, Immunoblotting, Ligands, Mice, Mice, Inbred BALB C, Nerve Tissue Proteins, Nuclear Proteins, Period Circadian Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Retinoic Acid, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Retinoid X Receptors, Trans-Activators, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques
Cell
Date: Jun. 29, 2001
Download Curated Data For This Publication
7170
Switch View:
  • Interactions 15