Identification of negative transcriptional factor E4BP4-binding site in the mouse circadian-regulated gene Mdr2

被引：12

作者：

Kotaka, Maki ^{[1
,2
]}

Onishi, Yoshiaki ^{[1
]}

Ohno, Tomoya ^{[1
,3
]}

Akaike, Toshihiro ^{[2
]}

Ishida, Norio ^{[1
,3
]}

机构：

[1] Natl Inst Adv Ind Sci & Technol, Clock Cell Biol Res Grp, Inst Biol Resources & Funct, Tsukuba, Ibaraki 3058566, Japan

[2] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biomol Engn, Yokohama, Kanagawa 2268501, Japan

[3] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 3058502, Japan

来源：

NEUROSCIENCE RESEARCH | 2008年 / 60卷 / 03期

关键词：

circadian; multidrug resistance 2 (Mdr2); ATP-binding cassette (ABC) transporter; E4BP4; negative transcription; cis-Element;

D O I：

10.1016/j.neures.2007.11.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

The hepatic transporter Mdr2 is an ATP-binding cassette transporter which excretes phosphatidylcholine into the bile. We showed that the level of Mdr2 mRNA oscillated in circadian fashion in mouse liver whereas such oscillation was dampened in the liver of Clock mutants. To examine transcriptional regulation of the Mdr2 gene we performed luciferase reporter assays using plasmid constructs containing the 5'-flanking region of the Mdr2 gene. Reporter assays using deletion constructs demonstrated that E4BP4 represses the transcriptional activity of the promoter including the D1 and D2 sites within four putative E4BP4-binding sites. Chromatin immunoprecipitation and gel shift assays showed that E4BP4 binds to the D2 site, but not to the D1 site. These data suggested that E4BP4 is a negative transcription factor for circadian Mdr2 mRNA expression. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

引用

页码：307 / 313

页数：7

共 43 条

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