title: Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism.
abstract: Circadian rhythms are intimately linked to cellular metabolism. Specifically, the NAD(+)-dependent deacetylase SIRT1, the founding member of the sirtuin family, contributes to clock function. Whereas SIRT1 exhibits diversity in deacetylation targets and subcellular localization, SIRT6 is the only constitutively chromatin-associated sirtuin and is prominently present at transcriptionally active genomic loci. Comparison of the hepatic circadian transcriptomes reveals that SIRT6 and SIRT1 separately control transcriptional specificity and therefore define distinctly partitioned classes of circadian genes. SIRT6 interacts with CLOCK:BMAL1 and, differently from SIRT1, governs their chromatin recruitment to circadian gene promoters. Moreover, SIRT6 controls circadian chromatin recruitment of SREBP-1, resulting in the cyclic regulation of genes implicated in fatty acid and cholesterol metabolism. This mechanism parallels a phenotypic disruption in fatty acid metabolism in SIRT6 null mice as revealed by circadian metabolome analyses. Thus, genomic partitioning by two independent sirtuins contributes to differential control of circadian metabolism.
authors.affiliation: Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Selma
authors.initials: S
authors.lastname: Masri
authors.affiliation: Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Rigor
authors.affiliation: Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Cervantes
authors.affiliation: Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ceglia
authors.affiliation: The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sebastian
authors.affiliation: Genetics of Development and Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Metabolic Disease Program, Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Roqueta-Rivera
authors.affiliation: Genetics of Development and Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.affiliation: Metabolic Disease Program, Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Osborne
authors.affiliation: The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Mostoslavsky
authors.affiliation: Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.affiliation: Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92697, USA; INSERM U904, Sprague Hall, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: psc@uci.edu.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism; D002843:Chromatin; D002940:Circadian Rhythm; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D002843:Chromatin; D056926:CLOCK Proteins; C538944:Clock protein, mouse; C501860:Sirt6 protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins
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