Genome-wide analysis of SREBP1 activity around the clock reveals its combined dependency on nutrient and circadian signals.

Détails

Ressource 1Télécharger: BIB_3BEC48D77E63.P001.pdf (1995.84 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_3BEC48D77E63
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genome-wide analysis of SREBP1 activity around the clock reveals its combined dependency on nutrient and circadian signals.
Périodique
PLoS Genetics
Auteur(s)
Gilardi F., Migliavacca E., Naldi A., Baruchet M., Canella D., Le Martelot G., Guex N., Desvergne B.
Collaborateur(s)
CycliX Consortium
Contributeur(s)
Hernandez N., Delorenzi M., Deplancke B., Desvergne B., Guex N., Herr W., Naef F., Rougemont J., Schibler U., Deplancke B., Guex N., Herr W., Guex N., Andersin T., Cousin P., Gilardi F., Gos P., Martelot G., Lammers F., Canella D., Gilardi F., Raghav S., Fabbretti R., Fortier A., Long L., Vlegel V., Xenarios I., Migliavacca E., Praz V., Guex N., Naef F., Rougemont J., David F., Jarosz Y., Kuznetsov D., Liechti R., Martin O., Delafontaine J., Sinclair L., Cajan J., Krier I., Leleu M., Migliavacca E., Molina N., Naldi A., Rey G., Symul L., Guex N., Naef F., Rougemont J., Bernasconi D., Delorenzi M., Andersin T., Canella D., Gilardi F., Martelot G., Lammers F., Baruchet£££Michaël£££ M. , Raghav S.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Statut éditorial
Publié
Date de publication
2014
Volume
10
Numéro
3
Pages
e1004155
Langue
anglais
Résumé
In mammals, the circadian clock allows them to anticipate and adapt physiology around the 24 hours. Conversely, metabolism and food consumption regulate the internal clock, pointing the existence of an intricate relationship between nutrient state and circadian homeostasis that is far from being understood. The Sterol Regulatory Element Binding Protein 1 (SREBP1) is a key regulator of lipid homeostasis. Hepatic SREBP1 function is influenced by the nutrient-response cycle, but also by the circadian machinery. To systematically understand how the interplay of circadian clock and nutrient-driven rhythm regulates SREBP1 activity, we evaluated the genome-wide binding of SREBP1 to its targets throughout the day in C57BL/6 mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding pattern. In particular, different expression phases were observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. Binding sites for Hepatocyte Nuclear Factor 4 (HNF4) were specifically enriched in the close proximity of SREBP1 peaks of genes, whose expression was shifted by about 8 hours with respect to SREBP1 binding. Thus, the cross-talk between hepatic HNF4 and SREBP1 may underlie the expression timing of this subgroup of SREBP1 targets. Interestingly, the proper temporal expression profile of these genes was dramatically changed in Bmal1-/- mice upon time-restricted feeding, for which a rhythmic, but slightly delayed, binding of SREBP1 was maintained. Collectively, our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity, strongly dependent from the circadian clock, exists. This system allows us to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved.
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/07/2014 10:41
Dernière modification de la notice
08/05/2019 17:21
Données d'usage