Circadian control of epigenetic modifications modulates metabolism. Subtitle: Circadian HDAC3/NCoR recruitment to DNA regulates hepatic lipid homeostasis

Numerous physiological processes (including sleep/wake cycles, body temperature, blood pressure, hormone secretion, metabolic pathways, etc display diurnal variations. These circadian rhythms are programmed centrally by light, allowing alignment to seasonal variations of night/day cycles, and peripherally by food availability. Disruption of these circadian rhythms (due to frequent jetlag, sleep restriction or rotating shift work) predisposes to metabolic disorders and cardiovascular diseases 1 . Genome-wide studies indicate that the expression of 10-15% of genes cycles in many organs involved in metabolic control, such as the liver, and cardiovascular function, such as the vascular wall and the heart. Although many of the transcription factors of the clock machinery also exert metabolic regulatory activities, the molecular mechanisms driving the rhythmic expression pattern of metabolic genes have been unclear until now.

[1]  Tao Liu,et al.  A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism , 2011, Science.

[2]  BartStaels,et al.  Nuclear Receptors Linking Circadian Rhythms and Cardiometabolic Control , 2010 .

[3]  M. Young,et al.  The cardiomyocyte circadian clock: emerging roles in health and disease. , 2010, Circulation research.

[4]  Ueli Schibler,et al.  REV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis , 2009, PLoS biology.

[5]  J. Viikari,et al.  Shift work in young adults and carotid artery intima-media thickness: The Cardiovascular Risk in Young Finns study. , 2009, Atherosclerosis.

[6]  G. Reed,et al.  Vascular Disease in Mice With a Dysfunctional Circadian Clock , 2009, Circulation.

[7]  F. Gonzalez,et al.  Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1. , 2008, Cell metabolism.

[8]  M. Bucan,et al.  Nuclear Receptor Corepressor-Histone Deacetylase 3 Governs Circadian Metabolic Physiology , 2008, Nature.

[9]  C. Fontaine,et al.  Regulation of bile acid synthesis by the nuclear receptor Rev-erbalpha. , 2008, Gastroenterology.

[10]  C. Fontaine,et al.  The nuclear receptor Rev-erbalpha is a liver X receptor (LXR) target gene driving a negative feedback loop on select LXR-induced pathways in human macrophages. , 2008, Molecular endocrinology.

[11]  M. Lazar,et al.  Bifunctional Role of Rev-erbα in Adipocyte Differentiation , 2008, Molecular and Cellular Biology.

[12]  M. Lazar,et al.  The Orphan Nuclear Receptor Rev-erbα Regulates Circadian Expression of Plasminogen Activator Inhibitor Type 1* , 2006, Journal of Biological Chemistry.

[13]  E. Raspé,et al.  Identification of Rev-erbalpha as a physiological repressor of apoC-III gene transcription. , 2002, Journal of lipid research.

[14]  Ueli Schibler,et al.  The Orphan Nuclear Receptor REV-ERBα Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator , 2002, Cell.

[15]  R. A. Reid,et al.  Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. , 2007, Science.

[16]  S. Mandrup,et al.  The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation. , 2003, The Journal of biological chemistry.