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

Hidenori Shirai; Katsutaka Oishi; Norio Ishida

doi:10.1016/j.bbrc.2006.10.031

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

Biochem Biophys Res Commun. 2006 Dec 15;351(2):387-91. doi: 10.1016/j.bbrc.2006.10.031. Epub 2006 Oct 27.

Authors

Hidenori Shirai¹, Katsutaka Oishi, Norio Ishida

Affiliation

¹ 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.

PMID: 17069763
DOI: 10.1016/j.bbrc.2006.10.031

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ARNTL Transcription Factors
Animals
Arginine Vasopressin / biosynthesis
Basic Helix-Loop-Helix Transcription Factors / metabolism*
CLOCK Proteins
Cell Cycle Proteins / biosynthesis
Circadian Rhythm / physiology*
E-Box Elements / physiology
Eye Proteins / biosynthesis
Mice
NIH 3T3 Cells
Nuclear Proteins / biosynthesis
PPAR alpha / biosynthesis
Period Circadian Proteins
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism
Retinoic Acid Receptor alpha
Trans-Activators / metabolism*
Transcription Factors / biosynthesis
Transfection
Tretinoin / pharmacology
Tretinoin / physiology*
Up-Regulation

Substances

ARNTL Transcription Factors
Bmal1 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Cell Cycle Proteins
Eye Proteins
Nuclear Proteins
PPAR alpha
Per1 protein, mouse
Per2 protein, mouse
Period Circadian Proteins
Rara protein, mouse
Receptors, Retinoic Acid
Retinoic Acid Receptor alpha
Trans-Activators
Transcription Factors
Arginine Vasopressin
Tretinoin
CLOCK Proteins
Clock protein, mouse