Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Yoo SH 

PROVIDER: S-EPMC548324 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9391061 | biostudies-literature
| S-EPMC3798035 | biostudies-literature
| S-EPMC8168560 | biostudies-literature
| S-EPMC5651750 | biostudies-literature
| S-EPMC3695510 | biostudies-literature
| S-EPMC8080691 | biostudies-literature
| S-EPMC7571335 | biostudies-literature
| S-EPMC5668311 | biostudies-literature
| S-EPMC1356568 | biostudies-literature
| S-EPMC3395600 | biostudies-literature