Partitioning Circadian Transcription by SIRT6 Leads to Segregated Control of Cellular Metabolism
Open accessAbstract
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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Sirtuin activity is coupled to the circadian clock, with SIRT1 and SIRT6 regulating core clock transcription factors and the downstream circadian transcriptome.
“It is also worth noting that sirtuin activity is coupled to the circadian clock, whereby SIRT1 and SIRT6 regulate the activity of the core clock transcription factors and downstream circadian transcriptome8.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [8]
A rise of NAD+ levels is strongly correlated with sirtuin activation during fasting and caloric restriction.
“Moreover, a rise of NAD+ levels is strongly correlated with sirtuin activation during fasting and caloric restriction8,9.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [8]
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References 62 · Cited by 292
- Authors
- Masri, S., Rigor, P., Cervantes, M., Ceglia, N., Sebastian, C., Xiao, C., Roqueta-Rivera, M., Deng, C., Osborne, T. F., Mostoslavsky, R., Baldi, P., & Sassone-Corsi, P.
- Affiliations
- University of California, Irvine (US)
- National Institutes of Health (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 158
- Issue
- 3
- Pages
- 659-672
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5472354
- OpenAlex
- W2088469132
- Cited by
- 292
- References
- 62
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 12 · 2023: 19 · 2022: 28 · 2021: 32 · 2020: 22 · 2019: 28 · 2018: 23 · 2017: 33 · 2016: 37 · 2015: 28 · 2014: 5
- FWCI
- 16.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (R21AG043745, AG043745)
- National Cancer Institute (R01CA175727, P30CA062203)
- National Institute of General Medical Sciences (GM097899, F32GM097899)
- U.S. National Library of Medicine (LM-07443, LM010235, R01LM010235, T15LM007443)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SIRT6, SIRT1, circadian clock, circadian transcription, sirtuins, chromatin recruitment, Clock/BMAL1, SREBP1, fatty acid metabolism, cholesterol metabolism, liver transcriptome, NAD+-dependent deacetylation
- MeSH terms
- Animals, Chromatin, Circadian Rhythm, Liver, Transcription, Genetic, Mice, Knockout, Gene Expression Profiling, Sirtuins, Mice, Sirtuin 1, CLOCK Proteins, ARNTL Transcription Factors
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