Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus
Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus
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DOI：
10.1016/s0960-9822(02)00759-5
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发表时间：
2002-04-02
期刊：
影响因子：
9.2
通讯作者：
Kyriacou, CP
中科院分区：
文献类型：
--
作者：
Akhtar, RA;Reddy, AB;Kyriacou, CP
背景：哺乳动物下丘脑视交叉上核（SCN）中编码生物钟起搏器的基因最近已被确定，但外周组织中生物钟计时的分子基础尚未被充分了解。我们使用定制的cDNA微阵列来识别在恒定条件下呈现丰度昼夜节律循环的小鼠肝脏转录本。
结果：通过两种独立的组织取样和杂交方案，我们表明在所研究的2122个基因中约9%在肝脏中呈现出明显的昼夜节律循环。这些转录本根据其丰度阶段进行分类，定义了与白天和夜晚相关的基因簇，同时也根据其产物的功能进行分类。基因的昼夜节律调节具有组织特异性，因为新的节律性肝脏基因在大脑中不一定有节律，即使在SCN中表达也是如此。然而，外周的节律性转录组依赖于SCN，因为手术切除SCN会严重减弱或完全破坏经典生物钟基因以及通过微阵列分析所确定的新基因的周期性表达。
结论：外周器官中转录组在时间上复杂的昼夜节律编程贯穿于广泛的核心细胞功能，并且依赖于内在的组织特异性因素与SCN中央起搏器的外在调节之间的相互作用。
Background: Genes encoding the circadian pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) of mammals have recently been identified, but the molecular basis of circadian timing in peripheral tissue is not well understood. We used a custom-made cDNA microarray to identify mouse liver transcripts that show circadian cycles of abundance under constant conditions.Results: Using two independent tissue sampling and hybridization regimes, we show that similar to9% of the 2122 genes studied show robust circadian cycling in the liver. These transcripts were categorized by their phase of abundance, defining clusters of day- and night-related genes, and also by the function of their products. Circadian regulation of genes was tissue specific, insofar as novel rhythmic liver genes were not necessarily rhythmic in the brain, even when expressed in the SCN. The rhythmic transcriptome in the periphery is, nevertheless, dependent on the SCN because surgical ablation of the SCN severely dampened or destroyed completely, the cyclical expression of both canonical circadian genes and novel genes identified by microarray analysis.Conclusions: Temporally complex, circadian programming of the transcriptome in a peripheral organ is imposed across a wide range of core cellular functions and is dependent on an interaction between intrinsic, tissue-specific factors and extrinsic regulation by the SCN central pacemaker.