2006年3月
Feedback repression is required for mammalian circadian clock function
NATURE GENETICS
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- 巻
- 38
- 号
- 3
- 開始ページ
- 312
- 終了ページ
- 319
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ng1745
- 出版者・発行元
- NATURE PUBLISHING GROUP
Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive. Here, we developed a molecular genetic screen in mammalian cells to identify mutants of the circadian transcriptional activators CLOCK and BMAL1, which were uncoupled from CRYPTOCHROME (CRY)- mediated transcriptional repression. Notably, mutations in the PER-ARNT-SIM domain of CLOCK and the C terminus of BMAL1 resulted in synergistic insensitivity through reduced physical interactions with CRY. Coexpression of these mutant proteins in cultured fibroblasts caused arrhythmic phenotypes in population and single-cell assays. These data demonstrate that CRY-mediated repression of the CLOCK/BMAL1 complex activity is required for maintenance of circadian rhythmicity and provide formal proof that transcriptional feedback is required for mammalian clock function.
- リンク情報
- ID情報
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- DOI : 10.1038/ng1745
- ISSN : 1061-4036
- PubMed ID : 16474406
- Web of Science ID : WOS:000235589600012