CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.
Détails
ID Serval
serval:BIB_0050828FF1AB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.
Périodique
Molecular and Cellular Biology
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Statut éditorial
Publié
Date de publication
2014
Volume
34
Numéro
10
Pages
1776-1787
Langue
anglais
Résumé
In mammalian circadian clockwork, the CLOCK-BMAL1 complex binds to DNA enhancers of target genes and drives circadian oscillation of transcription. Here we identified 7,978 CLOCK-binding sites in mouse liver by chromatin immunoprecipitation-sequencing (ChIP-Seq), and a newly developed bioinformatics method, motif centrality analysis of ChIP-Seq (MOCCS), revealed a genome-wide distribution of previously unappreciated noncanonical E-boxes targeted by CLOCK. In vitro promoter assays showed that CACGNG, CACGTT, and CATG(T/C)G are functional CLOCK-binding motifs. Furthermore, we extensively revealed rhythmically expressed genes by poly(A)-tailed RNA-Seq and identified 1,629 CLOCK target genes within 11,926 genes expressed in the liver. Our analysis also revealed rhythmically expressed genes that have no apparent CLOCK-binding site, indicating the importance of indirect transcriptional and posttranscriptional regulations. Indirect transcriptional regulation is represented by rhythmic expression of CLOCK-regulated transcription factors, such as Krüppel-like factors (KLFs). Indirect posttranscriptional regulation involves rhythmic microRNAs that were identified by small-RNA-Seq. Collectively, CLOCK-dependent direct transactivation through multiple E-boxes and indirect regulations polyphonically orchestrate dynamic circadian outputs.
Mots-clé
Animals, Base Sequence, Binding Sites, CLOCK Proteins/physiology, Circadian Rhythm, Consensus Sequence, E-Box Elements, HEK293 Cells, Humans, Kruppel-Like Transcription Factors/metabolism, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs/genetics, MicroRNAs/metabolism, Protein Binding, RNA Interference, Transcriptome
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/03/2014 12:40
Dernière modification de la notice
20/08/2019 12:22