CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.
Data(s) |
2014
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Resumo |
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. |
Identificador |
https://serval.unil.ch/?id=serval:BIB_0050828FF1AB isbn:1098-5549 (Electronic) pmid:24591654 doi:10.1128/MCB.01465-13 isiid:000334922400005 |
Idioma(s) |
en |
Fonte |
Molecular and Cellular Biology, vol. 34, no. 10, pp. 1776-1787 |
Palavras-Chave | #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 |
Tipo |
info:eu-repo/semantics/article article |