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

Kriebs, Anna; Jordan, Sabine D.; Soto, Erin; Henriksson, Emma LU ; Sandate, Colby R.; Vaughan, Megan E.; Chan, Alanna B.; Duglan, Drew; Papp, Stephanie J. and Huber, Anne Laure, et al. (2017) In Proceedings of the National Academy of Sciences of the United States of America 114(33). p.8776-8781
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,... (More)

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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Contribution to journal
publication status
published
subject
keywords
Circadian, Corepressor, Cryptochrome, Nuclear hormone receptor, Xenobiotic metabolism
in
Proceedings of the National Academy of Sciences of the United States of America
volume
114
issue
33
pages
6 pages
publisher
National Acad Sciences
external identifiers
  • scopus:85027396367
  • wos:000407610400061
ISSN
0027-8424
DOI
10.1073/pnas.1704955114
language
English
LU publication?
yes
id
41515e62-5f8d-4362-acd1-8472f259a605
date added to LUP
2017-08-29 12:54:30
date last changed
2018-05-20 04:36:49
@article{41515e62-5f8d-4362-acd1-8472f259a605,
  abstract     = {<p>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.</p>},
  author       = {Kriebs, Anna and Jordan, Sabine D. and Soto, Erin and Henriksson, Emma and Sandate, Colby R. and Vaughan, Megan E. and Chan, Alanna B. and Duglan, Drew and Papp, Stephanie J. and Huber, Anne Laure and Afetian, Megan E. and Yu, Ruth T. and Zhao, Xuan and Downes, Michael and Evans, Ronald M. and Lamia, Katja A},
  issn         = {0027-8424},
  keyword      = {Circadian,Corepressor,Cryptochrome,Nuclear hormone receptor,Xenobiotic metabolism},
  language     = {eng},
  month        = {08},
  number       = {33},
  pages        = {8776--8781},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and modulate transcriptional activity},
  url          = {http://dx.doi.org/10.1073/pnas.1704955114},
  volume       = {114},
  year         = {2017},
}