| First Author | Gekakis N | Year | 1998 |
| Journal | Science | Volume | 280 |
| Issue | 5369 | Pages | 1564-9 |
| PubMed ID | 9616112 | Mgi Jnum | J:48067 |
| Mgi Id | MGI:1261693 | Doi | 10.1126/science.280.5369.1564 |
| Citation | Gekakis N, et al. (1998) Role of the CLOCK protein in the mammalian circadian mechanism [see comments]. Science 280(5369):1564-9 |
| abstractText | The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors that act as heterodimers. Potential partners of CLOCK were isolated in a two-hybrid screen, and one, BMAL1, was coexpressed with CLOCK and PER1 at known circadian clock sites in brain and retina. CLOCK-BMAL1 heterodimers activated transcription from E-box elements, a type of transcription factor-binding site, found adjacent to the mouse per1 gene and from an identical E-box known to be important for per gene expression in Drosophila. Mutant CLOCK from the dominant-negative Clock allele and BMAL1 formed heterodimers that bound DNA but failed to activate transcription. Thus, CLOCK-BMAL1 heterodimers appear to drive the positive component of per transcriptional oscillations, which are thought to underlie circadian rhythmicity. |
