The genomic landscape of human cellular circadian variation points to a novel role for the signalosome.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_E8E1A136A4E5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The genomic landscape of human cellular circadian variation points to a novel role for the signalosome.
Périodique
eLife
Auteur(s)
Gaspar L., Howald C., Popadin K., Maier B., Mauvoisin D., Moriggi E., Gutierrez-Arcelus M., Falconnet E., Borel C., Kunz D., Kramer A., Gachon F., Dermitzakis E.T., Antonarakis S.E., Brown S.A.
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Statut éditorial
Publié
Date de publication
04/09/2017
Peer-reviewed
Oui
Volume
6
Pages
1-23
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome. We further show that the signalosome complex is imported into the nucleus in timed fashion to stabilize the essential circadian protein BMAL1, a novel mechanism to oppose its proteasome-mediated degradation. Thus, circadian clock properties depend in part upon a genetically-encoded competition between stabilizing and destabilizing forces, and genetic alterations in these mechanisms provide one explanation for human chronotype.
Mots-clé
ARNTL Transcription Factors/metabolism, Biological Variation, Population, COP9 Signalosome Complex/metabolism, Circadian Rhythm, Gene Expression Regulation, Genetic Variation, Genome-Wide Association Study, Humans, Protein Stability, Proteins/metabolism, cell biology, circadian, fibroblast, genetic variation, genome-wide association, human, protein stability, signalosome
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/09/2017 10:15
Dernière modification de la notice
20/08/2019 16:11
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