Specificity in circadian clock feedback from targeted reconstitution of the NuRD corepressor
Open accessAbstract
Mammalian circadian rhythms are generated by a negative feedback loop in which PERIOD (PER) proteins accumulate, form a large nuclear complex (PER complex), and bind the transcription factor CLOCK-BMAL1, repressing their own expression. We found that mouse PER complexes include the Mi-2/nucleosome remodelling and deacetylase (NuRD) transcriptional corepressor. Unexpectedly, two NuRD subunits, CHD4 and MTA2, constitutively associate with CLOCK-BMAL1, with CHD4 functioning to promote CLOCK-BMAL1 transcriptional activity. At the onset of negative feedback, the PER complex delivers the remaining complementary NuRD subunits to DNA-bound CLOCK-BMAL1, thereby reconstituting a NuRD corepressor that is important for circadian transcriptional feedback and clock function. The PER complex thus acquires full repressor activity only upon successful targeting of CLOCK-BMAL1. Our results show how specificity is generated in the clock despite its dependence on generic transcriptional regulators and reveal the existence of active communication between the positive and negative limbs of the circadian feedback loop.
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Chromatin and nucleosome remodeling contribute to circadian rhythm control independently of metabolism.
“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 Kim et al., 2014
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- Authors
- Kim, J. Y., Kwak, P. B., & Weitz, C. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Weitz, Charles J.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 56
- Issue
- 6
- Pages
- 738-748
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1997932809
- Cited by
- 96
- References
- 45
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 13 · 2018: 9 · 2017: 17 · 2016: 11 · 2015: 8 · 2014: 2
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- circadian clock, CHD4, MTA2, Clock/BMAL1, transcriptional repression, chromatin remodeling, deacetylase, reconstitution, clock gene expression
- MeSH terms
- Animals, Liver, Promoter Regions, Genetic, Protein Binding, Mice, Knockout, Protein Subunits, Feedback, Physiological, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Circadian Clocks
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