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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 33; pp. 8776 - 8781
• Main Authors: Kriebs, Anna, Jordan, Sabine D., Soto, Erin, Henriksson, Emma, Sandate, Colby R., Vaughan, Megan E., Chan, Alanna B., Duglan, Drew, Papp, Stephanie J., Huber, Anne-Laure, Afetian, Megan E., Yu, Ruth T., Zhao, Xuan, Downes, Michael, Evans, Ronald M., Lamia, Katja A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.08.2017
• Subjects: Animals; ARNTL Transcription Factors - metabolism; Biological clocks; Biological Sciences; BMAL1 protein; Brain; Cell Line; Cell Line, Tumor; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; CLOCK Proteins - metabolism; Control theory; Cryptochromes; Cryptochromes - metabolism; Diurnal; Drug metabolism; Feedback; Feedback loops; Feedback, Physiological - physiology; Female; Gene Expression Regulation - physiology; HEK293 Cells; Hep G2 Cells; Hormones; Humans; Lipophilic; Male; Mammals; Metabolism; Mice; Nuclear Proteins - metabolism; Nuclear receptors; Period Circadian Proteins - metabolism; Physiology; Receptors; Receptors, Cytoplasmic and Nuclear - metabolism; Repressors; Trans-Activators - metabolism; Transcription factors; Transcription, Genetic - physiology; circadian; xenobiotic metabolism; corepressor; cryptochrome; nuclear hormone receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1704955114

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.