title: The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2.
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.
authors.affiliation: Clock 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.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ohno
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Onishi
authors.forename: Norio
authors.initials: N
authors.lastname: Ishida
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000502:physiology*; D002522:Chlorocebus aethiops; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D056931:Cryptochromes; D005420:Flavoproteins / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000502:physiology*; D056950:Period Circadian Proteins; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D005420:Flavoproteins; C497441:Nfil3 protein, mouse; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors