CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes
| Autor: | Shigeki Shimba, Yutaka Suzuki, Wataru Iwasaki, Naoki Kosaka, Hideki Terajima, Yoshitaka Fukada, Haruka Ozaki, Hikari Yoshitane, Ngoc-Hien Du, Taihei Fujimori, Toshihisa Takagi, Sumio Sugano |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Kruppel-Like Transcription Factors CLOCK Proteins Biology E-Box Elements Transactivation Mice Transcription (biology) Consensus Sequence Transcriptional regulation Animals Humans Enhancer Molecular Biology Transcription factor Gene Genetics Mice Knockout Binding Sites Base Sequence Cell Biology Articles Chromatin Cell biology Circadian Rhythm Mice Inbred C57BL MicroRNAs HEK293 Cells Liver RNA Interference Transcriptome Protein Binding |
| Zdroj: | Molecular and cellular biology. 34(10) |
| ISSN: | 1098-5549 |
| Popis: | 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 Kruppel-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. |
| Databáze: | OpenAIRE |
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