Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism

Citation
S. Mitsui et al., Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism, GENE DEV, 15(8), 2001, pp. 995-1006
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
GENES & DEVELOPMENT
ISSN journal
0890-9369 → ACNP
Volume
15
Issue
8
Year of publication
2001
Pages
995 - 1006
Database
ISI
SICI code
0890-9369(20010415)15:8<995:AROEAP>2.0.ZU;2-D
Abstract
E4BP4, a basic leucine zipper transcription factor, contains a DNA-binding domain closely related to DBP, HLF, and TEF, which are PAR proteins. Here, rye show that the phase of e4bp4 mRNA rhythm is opposite to that of the dbp , hlf, and tef rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, and the Liver. The protein levels of E4BP4 and DBP also f luctuate in almost the opposite phase. Moreover, all PAR proteins activate, whereas E4BP4 suppresses, the transcriptional activity of the reporter gen e containing a common binding sequence in transcriptional assays in vitro. An electrophoretic mobility shift assay demonstrated that E4BP4 is not able to dimerize with the PAR proteins, but is able to compete for the same bin ding sites with them. Furthermore, we showed sustained low e4bp4 and high d bp mRNA levels in mCry-deficient mice. These results indicate that the E4BP 4 and PAR proteins are paired components of a reciprocating mechanism where in E4BP4 suppresses the transcription of target genes during the time of da y when E4BP4 is abundant, and the PAR proteins activate them at another tim e of day. E4BP4 and the PAR proteins may switch back and forth between the on-off conditions of the target genes.