Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback
Open accessAbstract
Circadian rhythms in mammals are driven by a feedback loop in which the transcription factor Clock-Bmal1 activates expression of Per and Cry proteins, which together form a large nuclear complex (Per complex) that represses Clock-Bmal1 activity. We found that mouse Clock-Bmal1 recruits the Ddb1-Cullin-4 ubiquitin ligase to Per (Per1 and Per2), Cry (Cry1 and Cry2) and other circadian target genes. Histone H2B monoubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1 and Cullin-4a. Depletion of Ddb1-Cullin-4a or an independent decrease in H2B monoubiquitination caused defective circadian feedback and decreased the association of the Per complex with DNA-bound Clock-Bmal1. Clock-Bmal1 thus covalently marks Per genes for subsequent recruitment of the Per complex. Our results reveal a chromatin-mediated signal from the positive to the negative limb of the clock that provides a licensing mechanism for circadian feedback.
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“Independently of metabolism, chromatin and nucleosome remodeling are important contributors to the control of circadian rhythm (Kim et al., 2014; Tamayo et al., 2015).”
From The Aging Epigenome (2016) · cites this paper as Tamayo et al., 2015
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- Authors
- Tamayo, A. G., Duong, H. A., Robles, M. S., Mann, M., & Weitz, C. J.
- Affiliations
- Harvard University (US)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Weitz, Charles J
- Venue
- Nature Structural & Molecular Biology
- Published
- 2015-08-31
- Volume
- 22
- Issue
- 10
- Pages
- 759-766
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC4600324
- OpenAlex
- W1259627718
- Cited by
- 60
- References
- 64
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 7 · 2016: 9
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM095945)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- circadian clock, histone H2B monoubiquitination, Per1, Per2, CRY1, CRY2, chromatin modification, transcriptional repression
- MeSH terms
- Animals, Chromatography, Liquid, Circadian Rhythm, DNA-Binding Proteins, Histones, Mice, Inbred C57BL, Oligopeptides, Immunoblotting, DNA Primers, Feedback, Physiological, Cullin Proteins, Multiprotein Complexes, Chromatin Immunoprecipitation, Mice, Tandem Mass Spectrometry, Ubiquitination, CLOCK Proteins, ARNTL Transcription Factors, Period Circadian Proteins, Real-Time Polymerase Chain Reaction
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