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Publication : Bidirectional CLOCK/BMAL1-dependent circadian gene regulation by retinoic acid in vitro.

First Author  Shirai H Year  2006
Journal  Biochem Biophys Res Commun Volume  351
Issue  2 Pages  387-91
PubMed ID  17069763 Mgi Jnum  J:116557
Mgi Id  MGI:3694507 Doi  10.1016/j.bbrc.2006.10.031
Citation  Shirai H, et al. (2006) Bidirectional CLOCK/BMAL1-dependent circadian gene regulation by retinoic acid in vitro. Biochem Biophys Res Commun 351(2):387-91
abstractText  A central circadian clock located in the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus entrains peripheral clocks through both neural and humoral factors. Although candidates for entrainment factors have been described, their details remain obscure. Here, we screened ligands for nuclear receptors that affect CLOCK/BMAL1-dependent transactivation of the mouse Period1 (mPer1) gene in NIH3T3 cells. We found that retinoic acids (RAs) significantly up-regulate mPer1 expression in an E-box-dependent manner. We also found that RAs up-regulate the expression of other E-box-dependent circadian genes such as mPer2, arginine vasopressin (mAVP), and peroxisome proliferator-activated receptor alpha (mPPARalpha). Surprisingly, the effect of RAs on CLOCK/BMAL1 (E-box)-dependent mRNA expression was bidirectional and depended on the presence of exogenous retinoic acid receptor alpha (RARalpha). These results suggest that RAs regulate the CLOCK/BMAL1-dependent transcription of circadian genes in a complex manner.
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