title: CREM modulates the circadian expression of CYP51, HMGCR and cholesterogenesis in the liver.
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.
authors.affiliation: Centre for Functional Genomics and Bio-Chips, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
authors.forename: Jure
authors.initials: J
authors.lastname: Acimovic
authors.forename: Martina
authors.initials: M
authors.lastname: Fink
authors.forename: Denis
authors.initials: D
authors.lastname: Pompon
authors.forename: Ingemar
authors.initials: I
authors.lastname: Bjorkhem
authors.forename: Jun
authors.initials: J
authors.lastname: Hirayama
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
authors.forename: Marko
authors.initials: M
authors.lastname: Golicnik
authors.forename: Damjana
authors.initials: D
authors.lastname: Rozman
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D002940:Circadian Rhythm / Q000235:genetics; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D058886:Sterol 14-Demethylase
chemical_list: D020033:Protein Isoforms; D051786:Cyclic AMP Response Element Modulator; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; C548415:Cyp51 protein, mouse; D058886:Sterol 14-Demethylase; D006904:Hydroxymethylglutaryl-CoA Synthase