C-terminal binding protein (CtBP) activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila.
C-terminal binding protein (CtBP) activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila.
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DOI：
10.1371/journal.pone.0063113
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tanimura T
中科院分区：
文献类型：
--
作者：
Itoh TQ;Matsumoto A;Tanimura T
在果蝇中，时钟/周期异源二聚体(CLK/CyC)是生物钟基因的主要激活子，这些基因在其启动子区域含有E-box序列(以下简称E-box时钟基因)。虽然大量的研究已经研究了时钟基因的反馈调节，但对与CLK/CyC一起作用的其他因子知之甚少。在这里，我们证明了果蝇C末端结合蛋白(DCtBP)，一个转录辅助因子，参与调节E-box时钟基因。在体内，dCtBP在时钟细胞中的过表达延长或取消了昼夜运动节律，上调了E-box时钟基因的一个子集，周期(PER)、Vrille(VRI)和PAR结构域蛋白1ε(Pdp1ε)。DCtBP与clk共表达对PER、VRI、Pdp1ε和CwO的启动子活性也有不同程度的增强作用，但与clk的共表达无明显影响。当我们使用突变的dCtBP时，我们没有观察到这些时钟基因在体外的激活。这些结果表明，dCtBP通常通过E-box序列作为CLK/CyC的协同激活因子。
In Drosophila, CLOCK/CYCLE heterodimer (CLK/CYC) is the primary activator of circadian clock genes that contain the E-box sequence in their promoter regions (hereafter referred to as “E-box clock genes”). Although extensive studies have investigated the feedback regulation of clock genes, little is known regarding other factors acting with CLK/CYC. Here we show that Drosophila C-terminal binding protein (dCtBP), a transcriptional co-factor, is involved in the regulation of the E-box clock genes. In vivo overexpression of dCtBP in clock cells lengthened or abolished circadian locomotor rhythm with up-regulation of a subset of the E-box clock genes, period (per), vrille (vri), and PAR domain protein 1ε (Pdp1ε). Co-expression of dCtBP with CLK in vitro also increased the promoter activity of per, vri, Pdp1ε and cwo depending on the amount of dCtBP expression, whereas no effect was observed without CLK. The activation of these clock genes in vitro was not observed when we used mutated dCtBP which carries amino acid substitutions in NAD+ domain. These results suggest that dCtBP generally acts as a putative co-activator of CLK/CYC through the E-box sequence.
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