TY - JOUR
T1 - Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism
AU - Masri, Selma
AU - Rigor, Paul
AU - Cervantes, Marlene
AU - Ceglia, Nicholas
AU - Sebastian, Carlos
AU - Xiao, Cuiying
AU - Roqueta-Rivera, Manuel
AU - Deng, Chuxia
AU - Osborne, Timothy F.
AU - Mostoslavsky, Raul
AU - Baldi, Pierre
AU - Sassone-Corsi, Paolo
N1 - Funding Information:
We thank Katrin Chua for reagents and helpful discussions. We thank all members of the Sassone-Corsi lab and Melanie Oakes, Seung-Ah Chung, Valentina Ciobanu, Yuzo Kanomata, and Andrea Eckhart for helpful discussion and technical assistance. Funding for S.M. was provided by NIH postdoctoral fellowship GM097899. Funding for P.B. was provided by NSF (IIS-1321053) and NIH (LM010235 and LM07443). Financial support for P.S.-C. was provided by NIH (AG043745), Merieux Research Grant (53923), and Sirtris Pharmaceuticals (SP-48984).
PY - 2014/7/31
Y1 - 2014/7/31
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2014.06.050
DO - 10.1016/j.cell.2014.06.050
M3 - Article
C2 - 25083875
AN - SCOPUS:84905389924
SN - 0092-8674
VL - 158
SP - 659
EP - 672
JO - Cell
JF - Cell
IS - 3
ER -