Author/Editor		Ačimovič, Jure; Fink, Martina; Pompon, Denis; Bjorkhem, Ingemar; Hirayama, Jun; Sassone-Corsi, Paolo; Goličnik, Marko; Rozman, Damjana
Title		CREM modulates the circadian expression of CYP51, HMGCR, and cholesterogenesis in the liver
Type		članek
Source		Biochem Biophys Res Commun
Vol. and No.		Letnik 376, št. 1
Publication year		2008
Volume		str. 206-10
Language		eng
Abstract		We show for the first time that isoforms of the cAMP response element modulator Crem, regulate the circadian expression of Cyp51 and other cholesterogenic genes in the mouse liver. In the wild type mice the expression of Cyp51, Hmgs, Fpps, and Sqs is minimal between CT12 and CT16 and peaks between CT20 and CT24. Cyp51, Fpps, and Sqs lost the circadian behavior in Crem-/- livers while Hmgcr is phase advanced from CT20 to CT12. This coincides with a phase advance of lathosterol/cholesterol ratio, as detected by GC-MS. Overexpression of CREMtau and ICER has little effect on the Hmgcr proximal promoter while they influence expression from the CYP51 promoter. Our data indicate that Crem-dependent regulation of Cyp51 in the liver results in circadian expression of this gene. We propose that cAMP signaling might generally be involved in the circadian regulation of cholesterol synthesis on the periphery.
Descriptors		LIVER CHOLESTEROL CYTOCHROME P-450 CYCLIC AMP GENE EXPRESSION MICE CIRCADIAN RHYTHM PROMOTER REGIONS (GENETICS)