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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Anna Kriebs
  • Sabine D. Jordan
  • Erin Soto
  • Emma Henriksson
  • Colby R. Sandate
  • Megan E. Vaughan
  • Alanna B. Chan
  • Drew Duglan
  • Stephanie J. Papp
  • Anne Laure Huber
  • Megan E. Afetian
  • Ruth T. Yu
  • Xuan Zhao
  • Michael Downes
  • Ronald M. Evans
  • Katja A Lamia
Organisations
External organisations
  • Scripps Research Institute
  • Salk Institute for Biological Studies
  • University of California, San Diego
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology

Keywords

  • Circadian, Corepressor, Cryptochrome, Nuclear hormone receptor, Xenobiotic metabolism
Original languageEnglish
Pages (from-to)8776-8781
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number33
Publication statusPublished - 2017 Aug 15
Publication categoryResearch
Peer-reviewedYes