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Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):8776-8781. doi: 10.1073/pnas.1704955114. Epub 2017 Jul 27.

Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and modulate transcriptional activity.

Author information

1
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037.
2
Department of Clinical Sciences, Clinical Research Centre, Lund University, Malmö 20502, Sweden.
3
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037.
4
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037.
5
Center for Circadian Biology, University of California, San Diego, CA 92161.
6
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037; klamia@scripps.edu.

Abstract

Nuclear hormone receptors (NRs) regulate physiology by sensing lipophilic ligands and adapting cellular transcription appropriately. A growing understanding of the impact of circadian clocks on mammalian transcription has sparked interest in the interregulation of transcriptional programs. Mammalian clocks are based on a transcriptional feedback loop featuring the transcriptional activators circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1), and transcriptional repressors cryptochrome (CRY) and period (PER). CRY1 and CRY2 bind independently of other core clock factors to many genomic sites, which are enriched for NR recognition motifs. Here we report that CRY1/2 serve as corepressors for many NRs, indicating a new facet of circadian control of NR-mediated regulation of metabolism and physiology, and specifically contribute to diurnal modulation of drug metabolism.

KEYWORDS:

circadian; corepressor; cryptochrome; nuclear hormone receptor; xenobiotic metabolism

PMID:
28751364
PMCID:
PMC5565439
DOI:
10.1073/pnas.1704955114
[Indexed for MEDLINE]
Free PMC Article

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