PMID- 17069763 OWN - NLM STAT- MEDLINE DCOM- 20070119 LR - 20231213 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 351 IP - 2 DP - 2006 Dec 15 TI - Bidirectional CLOCK/BMAL1-dependent circadian gene regulation by retinoic acid in vitro. PG - 387-91 AB - 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. FAU - Shirai, Hidenori AU - Shirai H AD - Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. FAU - Oishi, Katsutaka AU - Oishi K FAU - Ishida, Norio AU - Ishida N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061027 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (ARNTL Transcription Factors) RN - 0 (Bmal1 protein, mouse) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Cell Cycle Proteins) RN - 0 (Eye Proteins) RN - 0 (Nuclear Proteins) RN - 0 (PPAR alpha) RN - 0 (Per1 protein, mouse) RN - 0 (Per2 protein, mouse) RN - 0 (Period Circadian Proteins) RN - 0 (Rara protein, mouse) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoic Acid Receptor alpha) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 113-79-1 (Arginine Vasopressin) RN - 5688UTC01R (Tretinoin) RN - EC 2.3.1.48 (CLOCK Proteins) RN - EC 2.3.1.48 (Clock protein, mouse) SB - IM MH - ARNTL Transcription Factors MH - Animals MH - Arginine Vasopressin/biosynthesis MH - Basic Helix-Loop-Helix Transcription Factors/*metabolism MH - CLOCK Proteins MH - Cell Cycle Proteins/biosynthesis MH - Circadian Rhythm/*physiology MH - E-Box Elements/physiology MH - Eye Proteins/biosynthesis MH - Mice MH - NIH 3T3 Cells MH - Nuclear Proteins/biosynthesis MH - PPAR alpha/biosynthesis MH - Period Circadian Proteins MH - Receptors, Retinoic Acid/genetics/metabolism MH - Retinoic Acid Receptor alpha MH - Trans-Activators/*metabolism MH - Transcription Factors/biosynthesis MH - Transfection MH - Tretinoin/pharmacology/*physiology MH - Up-Regulation EDAT- 2006/10/31 09:00 MHDA- 2007/01/20 09:00 CRDT- 2006/10/31 09:00 PHST- 2006/09/22 00:00 [received] PHST- 2006/10/08 00:00 [accepted] PHST- 2006/10/31 09:00 [pubmed] PHST- 2007/01/20 09:00 [medline] PHST- 2006/10/31 09:00 [entrez] AID - S0006-291X(06)02269-8 [pii] AID - 10.1016/j.bbrc.2006.10.031 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2006 Dec 15;351(2):387-91. doi: 10.1016/j.bbrc.2006.10.031. Epub 2006 Oct 27.