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

Jul 29, 2017Proceedings of the National Academy of Sciences of the United States of America

Circadian proteins CRY1 and CRY2 interact widely with gene regulators and influence gene activity

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Abstract

CRY1 and CRY2 serve as corepressors for many nuclear hormone receptors (NRs).

Circadian clocks influence transcriptional programs in mammals.
CRY1 and CRY2 bind to numerous genomic sites enriched for NR recognition motifs.
The interaction of CRY1/2 with NRs suggests a connection between circadian rhythms and metabolic regulation.
CRY1/2 may play a role in the daily modulation of drug metabolism.

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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.

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

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