| First Author | Cao X | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 2 | PubMed ID | 33443219 |
| Mgi Jnum | J:300048 | Mgi Id | MGI:6501251 |
| Doi | 10.1073/pnas.2021174118 | Citation | Cao X, et al. (2021) Molecular mechanism of the repressive phase of the mammalian circadian clock. Proc Natl Acad Sci U S A 118(2):e2021174118 |
| abstractText | The mammalian circadian clock consists of a transcription-translation feedback loop (TTFL) composed of CLOCK-BMAL1 transcriptional activators and CRY-PER transcriptional repressors. Previous work showed that CRY inhibits CLOCK-BMAL1-activated transcription by a "blocking"-type mechanism and that CRY-PER inhibits CLOCK-BMAL1 by a "displacement"-type mechanism. While the mechanism of CRY-mediated repression was explained by both in vitro and in vivo experiments, the CRY-PER-mediated repression in vivo seemed in conflict with the in vitro data demonstrating PER removes CRY from the CLOCK-BMAL1-E-box complex. Here, we show that CRY-PER participates in the displacement-type repression by recruiting CK1delta to the nucleus and mediating an increased local concentration of CK1delta at CLOCK-BMAL1-bound promoters/enhancers and thus promoting the phosphorylation of CLOCK and dissociation of CLOCK-BMAL1 along with CRY from the E-box. Our findings bring clarity to the role of PER in the dynamic nature of the repressive phase of the TTFL. |
