| First Author | Sato TK | Year | 2006 |
| Journal | Nat Genet | Volume | 38 |
| Issue | 3 | Pages | 312-9 |
| PubMed ID | 16474406 | Mgi Jnum | J:106794 |
| Mgi Id | MGI:3619612 | Doi | 10.1038/ng1745 |
| Citation | Sato TK, et al. (2006) Feedback repression is required for mammalian circadian clock function. Nat Genet 38(3):312-9 |
| abstractText | 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. |
