| First Author | Hirayama J | Year | 2007 |
| Journal | Nature | Volume | 450 |
| Issue | 7172 | Pages | 1086-90 |
| PubMed ID | 18075593 | Mgi Jnum | J:130591 |
| Mgi Id | MGI:3771941 | Doi | 10.1038/nature06394 |
| Citation | Hirayama J, et al. (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature 450(7172):1086-90 |
| abstractText | Regulation of circadian physiology relies on the interplay of interconnected transcriptional-translational feedback loops. The CLOCK-BMAL1 complex activates clock-controlled genes, including cryptochromes (Crys), the products of which act as repressors by interacting directly with CLOCK-BMAL1. We have demonstrated that CLOCK possesses intrinsic histone acetyltransferase activity and that this enzymatic function contributes to chromatin-remodelling events implicated in circadian control of gene expression. Here we show that CLOCK also acetylates a non-histone substrate: its own partner, BMAL1, is specifically acetylated on a unique, highly conserved Lys 537 residue. BMAL1 undergoes rhythmic acetylation in mouse liver, with a timing that parallels the downregulation of circadian transcription of clock-controlled genes. BMAL1 acetylation facilitates recruitment of CRY1 to CLOCK-BMAL1, thereby promoting transcriptional repression. Importantly, ectopic expression of a K537R-mutated BMAL1 is not able to rescue circadian rhythmicity in a cellular model of peripheral clock. These findings reveal that the enzymatic interplay between two clock core components is crucial for the circadian machinery. |
