TY - JOUR
T1 - Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature
T2 - A humoral mechanism to reset a peripheral clock
AU - McNamara, Peter
AU - Seo, Sang beom
AU - Rudic, Radu Daniel
AU - Sehgal, Amita
AU - Chakravarti, Debabrata
AU - FitzGerald, Garret A.
N1 - Funding Information:
We thank Drs. M. McDonnell and T. Grosser for critical reading of the manuscript, continuous support, helpful suggestions, and encouragement. We also thank E. V. Kostetskaia for her technical assistance. We are grateful to Drs. C. Bradfield and J. Hogenesch for MOP4, CLOCK, and MOP3 cDNA clones and for the M34-Luc reporter vector; S. McKnight for the NPAS2 cDNA clone. We also thank Drs. J. Mulldowney, P. Hahn, and P. Ghoroghchian for help during the initial phase of the project. This work was supported by National Institutes of Health research grants (SCOR, 1P50HL54500 and PO1 HL62250-01 to G.A.F., and RO1-DK57079-01A1 to D.C.). A.S. is an Associate Investigator in the HHMI.
PY - 2001/6/29
Y1 - 2001/6/29
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(01)00401-9
DO - 10.1016/S0092-8674(01)00401-9
M3 - Article
C2 - 11439184
AN - SCOPUS:0035967914
SN - 0092-8674
VL - 105
SP - 877
EP - 889
JO - Cell
JF - Cell
IS - 7
ER -