Coupling circadian rhythms of metabolism and chromatin remodelling.
The circadian clock controls a large variety of neuronal, endocrine, behavioural and physiological responses in mammals. This control is exerted in large part at the transcriptional level on genes expressed in a cyclic manner. A highly specialized transcriptional machinery based on clock regulatory factors organized in feedback autoregulatory loops governs a significant portion of the genome. These oscillations in gene expression are paralleled by critical events of chromatin remodelling that appear to provide plasticity to circadian regulation. Specifically, the nicotinamide adenine dinucleotide (NAD)(+) -dependent deacetylases SIRT1 and SIRT6 have been linked to circadian control of gene expression. This, and additional accumulating evidence, shows that the circadian epigenome appears to share intimate links with cellular metabolic processes and has remarkable plasticity showing reprogramming in response to nutritional challenges. In addition to SIRT1 and SIRT6, a number of chromatin remodellers have been implicated in clock control, including the histone H3K4 tri-methyltransferase MLL1. Deciphering the molecular mechanisms that link metabolism, epigenetic control and circadian responses will provide valuable insights towards innovative strategies of therapeutic intervention.
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
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S
Masri
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
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R
Orozco-Solis
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
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Aguilar-Arnal
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
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M
Cervantes
Center for Epigenetics and Metabolism, Unit 904 of INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
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Sassone-Corsi
D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics*; D002477:Cells / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002940:Circadian Rhythm / Q000235:genetics*; D057890:Epigenomics; D015870:Gene Expression; D006801:Humans; D008322:Mammals / Q000235:genetics*; D009243:NAD / Q000235:genetics / Q000378:metabolism; D009747:Nutritional Physiological Phenomena / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics; D037761:Sirtuins / Q000235:genetics; D014158:Transcription, Genetic
D009243:NAD; D056926:CLOCK Proteins; C447939:SIRT1 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D037761:Sirtuins
NAD+; chromatin remodelling; epigenetics; nutrition; sirtuins