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Publication : A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo.

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.
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