CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.

Details

Serval ID
serval:BIB_0050828FF1AB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.
Journal
Molecular and Cellular Biology
Author(s)
Yoshitane H., Ozaki H., Terajima H., Du N.H., Suzuki Y., Fujimori T., Kosaka N., Shimba S., Sugano S., Takagi T., Iwasaki W., Fukada Y.
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Publication state
Published
Issued date
2014
Volume
34
Number
10
Pages
1776-1787
Language
english
Abstract
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.
Keywords
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
Yes
Create date
06/03/2014 12:40
Last modification date
20/08/2019 12:22
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