| First Author | Shi G | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 4 | Pages | 823-834 |
| PubMed ID | 26776516 | Mgi Jnum | J:240095 |
| Mgi Id | MGI:5882311 | Doi | 10.1016/j.celrep.2015.12.076 |
| Citation | Shi G, et al. (2016) Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function. Cell Rep 14(4):823-34 |
| abstractText | In the core mammalian circadian negative feedback loop, the BMAL1-CLOCK complex activates the transcription of the genes Period (Per) and Cryptochrome (Cry). To close the negative feedback loop, the PER-CRY complex interacts with the BMAL1-CLOCK complex to repress its activity. These two processes are separated temporally to ensure clock function. Here, we show that histone deacetylase 3 (HDAC3) is a critical component of the circadian negative feedback loop by regulating both the activation and repression processes in a deacetylase activity-independent manner. Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription. In subjective morning, HDAC3 is required for the efficient transcriptional activation process by regulating BMAL1 stability. In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association. Therefore, these two opposing but temporally separated roles of HDAC3 in the negative feedback loop provide a mechanism for robust circadian gene expression. |
