Light-induced phase-delay of the chicken pineal circadian clock is associated with the induction of cE4bp4, a potential transcriptional repressor of cPer2 gene
Light-induced phase-delay of the chicken pineal circadian clock is associated with the induction of cE4bp4, a potential transcriptional repressor of cPer2 gene
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DOI：
10.1073/pnas.141090998
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发表时间：
2001-07-03
影响因子：
11.1
通讯作者：
Fukada, Y
中科院分区：
文献类型：
--
作者：
Doi, M;Nakajima, Y;Fukada, Y
鸡的松果体含有自主的昼夜节律振荡器和光输入通路。我们寻找鸡松果体基因，光诱导的一天中的时间依赖性的方式，并分离鸡同源的bZIP转录因子E4 bp 4（cE 4 bp 4）显示出高度的相似性vrille，果蝇的时钟基因之一。在12 h光照/12 h黑暗周期和恒定黑暗条件下，cE 4 bp 4在松果体中的表达均呈节律性，峰值均出现在极早的夜晚，其时相与鸡松果体时钟基因cPer 2的表达节律几乎相反。荧光素酶报告基因分析表明，cE 4 BP 4通过5 '端的E4 BP 4识别序列抑制cPer 2启动子的表达，表明cE 4 BP 4能下调鸡松果体cPer 2的表达。在体内光扰动的研究表明，光周期的延长到早期主观的夜晚保持高水平的表达的松果体cE 4 bp 4，并推测作为一个结果延迟发病的诱导松果体cPer 2的表达在第二天早上。松果体cE 46 p4和cPer 2 mRNA水平的这些光依赖性变化之后，cE 4 bp 4/cPer 2表达的后续周期的相位延迟，表明cE 4 BP 4作为cPer 2基因的光依赖性抑制因子在相位延迟过程中起重要作用。
The chicken pineal gland contains the autonomous circadian oscillator together with the photic-input pathway. We searched for chicken pineal genes that are induced by light in a time-of-day-dependent manner, and isolated chicken homolog of bZIP transcription factor E4bp4 (cE4bp4) showing high similarity to vrille, one of the Drosophila clock genes. cE4bp4 was expressed rhythmically in the pineal gland with a peak at very early (subjective) night under both 12-h light/12-h dark cycle and constant dark conditions, and the phase was nearly opposite to the expression rhythm of cPer2, a chicken pineal clock gene. Luciferase reporter gene assays showed that cE4BP4 represses cPer2 promoter through a E4BP4-recognition sequence present in the 5 ' -flanking region, indicating that cE4BP4 can down-regulate the chick pineal cPer2 expression. In vivo light-perturbation studies showed that the prolongation of the light period to early subjective night maintained the high level expression of the pineal cE4bp4, and presumably as a consequence delayed the onset of the induction of the pineal cPer2 expression in the next morning. These light-dependent changes in the mRNA levels of the pineal cE46p4 and cPer2 were followed by a phase-delay of the subsequent cycles of cE4bp4/cPer2 expression, suggesting that cE4BP4 plays an important role in the phase-delaying process as a light-dependent suppressor of cPer2 gene.