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Published on: September 28, 2017
The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2
Tomoya Ohno1, Yoshiaki Onishi, Norio Ishida
1Clock Cell Biology, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6-5, 1-1-1 Higashi, Tsukuba, Japan.
Abstract:
The bZIP transcription factor E4BP4, is a mammalian homologue of vrille that functions as a key negative component of the circadian clock. We have shown that the E4BP4-binding site (B-site) is required in addition to a non-canonical E-box (E2 enhancer) for robust circadian Period2 (Per2) expression in the cell-autonomous clock. While the E2 enhancer and the B-site are closely situated, correlations between each component bound to the E2 enhancer and the B-site remain obscure. Here, we show that E4BP4 interacts with PER2, which represses transcriptional activity via the E-box enhancer. Interaction with PER2 required the carboxyl-terminal region that contains the repression domain of E4BP4. We also found that E4BP4 interacts with CRYPTOCHROME2 (CRY2), a key negative regulator in the mammalian circadian clock. These results suggest that E4BP4 is a component of the negative regulator complex of mammalian circadian clocks.
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