期刊
COMMUNICATIONS BIOLOGY
卷 2, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s42003-019-0522-3
关键词
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资金
- PRIME from Japan Agency for Medical Research and Development [17937210]
- MEXT of Japan [17H06096, 24227001, 19H03175, 25440041, 15H01395]
- Grants-in-Aid for Scientific Research [19H03175, 17H06096, 25440041, 15H01395] Funding Source: KAKEN
The circadian clock drives gene expression rhythms, leading to daily changes in physiology and behavior. In mammals, Albumin D-site-Binding Protein (DBP) rhythmically activates transcription of various genes through a DNA cis-element, D-box. The DBP-dependent transactivation is repressed by competitive binding of E4BP4 to the D-box. Despite the elaborate regulation, physiological roles of the D-box in the circadian clockwork are still elusive. Here we identified 1490 genomic regions recognized commonly by DBP and E4BP4 in the mouse liver. We comprehensively defined functional D-box sequences using an improved bioinformatics method, MOCCS2. In RNA-Seq analysis of E4bp4-knockout and wild type liver, we showed the importance of E4BP4-mediated circadian repression in gene expression rhythms. In addition to the circadian control, we found that environmental stimuli caused acute induction of E4BP4 protein, evoking phase-dependent phase shifts of cellular circadian rhythms and resetting the clock. Collectively, D-box-mediated transcriptional regulation plays pivotal roles in input and output in the circadian clock system.
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