First Author | Yoo SH | Year | 2005 |
Journal | Proc Natl Acad Sci U S A | Volume | 102 |
Issue | 7 | Pages | 2608-13 |
PubMed ID | 15699353 | Mgi Jnum | J:152289 |
Mgi Id | MGI:4357870 | Doi | 10.1073/pnas.0409763102 |
Citation | Yoo SH, et al. (2005) A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo. Proc Natl Acad Sci U S A 102(7):2608-13 |
abstractText | The mouse Period2 (mPer2) locus is an essential negative-feedback element of the mammalian circadian-clock mechanism. Recent work has shown that mPer2 circadian gene expression persists in both central and peripheral tissues. Here, we analyze the mouse mPer2 promoter and identify a circadian enhancer (E2) with a noncanonical 5'-CACGTT-3' E-box located 20 bp upstream of the mPer2 transcription start site. The E2 enhancer accounts for most circadian transcriptional drive of the mPer2 locus by CLOCK:BMAL1, is a major site of DNaseI hypersensitivity in this region, and is constitutively bound by a transcriptional complex containing the CLOCK protein. Importantly, the E2 enhancer is sufficient to drive self-sustained circadian rhythms of luciferase activity in central and peripheral tissues from mPer2-E2::Luciferase transgenic mice with tissue-specific phase and period characteristics. Last, genetic analysis with mutations in Clock and Bmal1 shows that the E2 enhancer is a target of CLOCK and BMAL1 in vivo. |