RRC ID 52344
著者 Umemura Y, Koike N, Ohashi M, Tsuchiya Y, Meng QJ, Minami Y, Hara M, Hisatomi M, Yagita K.
タイトル Involvement of posttranscriptional regulation of Clock in the emergence of circadian clock oscillation during mouse development.
ジャーナル Proc Natl Acad Sci U S A
Abstract Circadian clock oscillation emerges in mouse embryo in the later developmental stages. Although circadian clock development is closely correlated with cellular differentiation, the mechanisms of its emergence during mammalian development are not well understood. Here, we demonstrate an essential role of the posttranscriptional regulation of Clock subsequent to the cellular differentiation for the emergence of circadian clock oscillation in mouse fetal hearts and mouse embryonic stem cells (ESCs). In mouse fetal hearts, no apparent oscillation of cell-autonomous molecular clock was detectable around E10, whereas oscillation was clearly visible in E18 hearts. Temporal RNA-sequencing analysis using mouse fetal hearts reveals many fewer rhythmic genes in E10-12 hearts (63, no core circadian genes) than in E17-19 hearts (483 genes), suggesting the lack of functional circadian transcriptional/translational feedback loops (TTFLs) of core circadian genes in E10 mouse fetal hearts. In both ESCs and E10 embryos, CLOCK protein was absent despite the expression of Clock mRNA, which we showed was due to Dicer/Dgcr8-dependent translational suppression of CLOCK. The CLOCK protein is required for the discernible molecular oscillation in differentiated cells, and the posttranscriptional regulation of Clock plays a role in setting the timing for the emergence of the circadian clock oscillation during mammalian development.
巻・号 114(36)
ページ E7479-E7488
公開日 2017-9-5
DOI 10.1073/pnas.1703170114
PII 1703170114
PMID 28827343
PMC PMC5594651
MeSH Animals CLOCK Proteins / genetics* Cell Differentiation / genetics Circadian Clocks / genetics* Circadian Rhythm / genetics* Gene Expression Regulation / genetics Mice Mouse Embryonic Stem Cells / metabolism* Period Circadian Proteins / genetics* Protein Processing, Post-Translational / genetics* RNA, Messenger / genetics RNA-Binding Proteins / genetics
IF 9.412
引用数 20
リソース情報
ヒト・動物細胞 mGS-DBA1(AES0004) iPS-MEF-Ng-178B-5(APS0002)