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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ARNTL Transcription Factors / metabolism
  • Animals
  • CLOCK Proteins / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Circadian Clocks / physiology
  • Circadian Rhythm / physiology*
  • Cryptochromes / metabolism*
  • Feedback, Physiological / physiology
  • Female
  • Gene Expression Regulation / physiology
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Male
  • Mice
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Trans-Activators / metabolism
  • Transcription, Genetic / physiology*


  • ARNTL Transcription Factors
  • CRY1 protein, human
  • CRY2 protein, human
  • Cryptochromes
  • Nuclear Proteins
  • Period Circadian Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • CLOCK Proteins