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首页> 外文期刊>Genes to cells : >Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP.
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Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP.

机译：DEC1和DEC2在周围组织中的节律性表达：DEC2是与DBP相对的肝细胞色素P450的有效抑制剂。

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摘要

The mammalian master molecular clock consisting of several clock gene products in the suprachiasmatic nucleus (SCN) drives circadian rhythms in behaviour and physiology. Molecular clocks consisting of the same components also exist in various peripheral organs. DEC1 and DEC2, basic helix-loop-helix transcription factors, were recently reported to be involved in the central clock in the SCN. We examined the expression profile of DEC1 and DEC2 in the periphery and their roles in the regulation of oscillating target genes in the liver. Levels of DEC1 and DEC2 mRNA exhibited a day-night variation in various peripheral tissues of rats. In the liver, their expression was high during the subjective night. Transfection assays showed that DEC2, but not DEC1, suppressed the transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A), overwhelming the potent enhancement by D-site binding protein (DBP). Electrophoretic mobility shift assays indicated that DEC2 binds to the E-box (CACATG) at the -219/-214 region of CYP7A. The transcriptional activities of the other sterol metabolizing cytochrome P450s (Cyps), CYP8B and CYP51, were also suppressed by DEC2 but not DEC1. DEC2, but not DEC1, works as a direct output mediator that transmits the circadian signals to the hepatic functions, including the CYP7A, CYP8B, and CYP51 expression.
机译：哺乳动物的主要分子钟由视交叉上核（SCN）中的几种时钟基因产物组成，可驱动行为和生理上的昼夜节律。由相同成分组成的分子钟也存在于各种外围器官中。最近报道，DEC1和DEC2是基本的螺旋-环-螺旋转录因子，参与了SCN的中央时钟。我们检查了周围的DEC1和DEC2的表达谱及其在肝脏中振荡靶基因调控中的作用。 DEC1和DEC2 mRNA的水平在大鼠的各种外周组织中表现出昼夜变化。在肝脏中，它们在主观的夜晚表达很高。转染测定法显示DEC2而非DEC1抑制胆固醇7α-羟化酶基因（CYP7A）的转录，从而抑制了D-位点结合蛋白（DBP）的有效增强作用。电泳迁移率迁移分析表明DEC2在CYP7A的-219 / -214区与E-box（CACATG）结合。其他固醇代谢细胞色素P450（Cyps），CYP8B和CYP51的转录活性也被DEC2抑制，但未被DEC1抑制。 DEC2（而非DEC1）充当直接输出介体，将昼夜节律信号传输至肝功能，包括CYP7A，CYP8B和CYP51表达。

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