| First Author | Li DQ | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2545 | PubMed ID | 24089055 |
| Mgi Jnum | J:213082 | Mgi Id | MGI:5582861 |
| Doi | 10.1038/ncomms3545 | Citation | Li DQ, et al. (2013) Metastasis-associated protein 1 is an integral component of the circadian molecular machinery. Nat Commun 4:2545 |
| abstractText | The mammalian circadian clock regulates the daily cycles of many important physiological processes, but its mechanism is not well understood. Here we provide genetic and biochemical evidence that metastasis-associated protein 1 (MTA1), a widely upregulated gene product in human cancers, is an integral component of the circadian molecular machinery. Knockout of MTA1 in mice disrupts the free-running period of circadian rhythms under constant light and normal entrainment of behaviour to 12-h-light/12-h-dark cycles. The CLOCK-BMAL1 heterodimer activates MTA1 transcription through a conserved E-box element at its promoter. MTA1, in turn, interacts with and recruits CLOCK-BMAL1 at its own and CRY1 promoters and promotes their transcription. Moreover, MTA1 deacetylates BMAL1 at lysine 538 through regulating deacetylase SIRT1 expression, thus disturbing the CRY1-mediated negative feedback loop. These findings uncover a previously unappreciated role for MTA1 in maintenance of circadian rhythmicity through acting on the positive limb of the clock machinery. |
