Genome-wide expression analysis reveals 100 adrenal gland-dependent circadian genes in the mouse liver
Genome-wide expression analysis reveals 100 adrenal gland-dependent circadian genes in the mouse liver
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DOI：
10.1093/dnares/dsi003
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发表时间：
2005-06-30
期刊：
影响因子：
4.1
通讯作者：
Ishida, Norio
中科院分区：
文献类型：
--
作者：
Oishi, Katsutaka;Amagai, Noriko;Ishida, Norio
近年来，全基因组表达分析已经发现了数百个昼夜节律基因，这些基因不仅存在于视交叉上核（哺乳动物的主时钟）中，还存在于哺乳动物的心脏、肝脏和肾脏等外周组织中。糖皮质激素被认为是哺乳动物外周时钟的昼夜节律时间线索。为了确定内源性糖皮质激素调节昼夜节律表达的基因，我们使用肾上腺切除（ADX）和假手术小鼠的肝脏RNA进行了DNA微阵列分析。我们在假手术小鼠的肝脏中发现了169个昼夜波动的基因。其中，100只ADX小鼠丧失了昼夜节律性。这些基因包括肝脏代谢功能关键酶的基因，如葡萄糖激酶、HMG-CoA还原酶和葡萄糖-6-磷酸酶。在ADX小鼠中，Lpin1、FKBP51和s -腺苷蛋氨酸脱羧酶的昼夜表达也被消除。另一方面，尽管时钟或时钟相关基因，如mPer2、DBP、E4BP4、mDec1、Usp2和Wee1在ADX小鼠肝脏中的昼夜节律表达几乎完全保持不变，但在纯合子时钟突变小鼠中却受到极大的抑制。目前的研究结果表明，小鼠肝脏的一种昼夜节律基因是由昼夜节律钟的核心成分（如clock和BMAL1）转录调节的，而另一种则依赖于肾上腺。
Recent progress in genome-wide expression analysis has identified hundreds of circadian genes not only in the suprachiasmatic nucleus (the mammalian master clock) but also in peripheral tissues, such as heart, liver and kidney of mammals. Glucocorticoid is thought to be a circadian time cue for mammalian peripheral clocks. To identify the genes of which the circadian expression is regulated by endogenous glucocorticoids, we performed DNA microarray analysis using hepatic RNA from adrenalectomized (ADX) and sham-operated mice. We identified 169 genes that fluctuated between day and night in the livers of the sham-operated mice. Among these, 100 lost circadian rhythmicity in ADX mice. These included the genes for key enzymes of liver metabolic functions, such as glucokinase, HMG-CoA reductase and glucose-6-phosphatase. The circadian expression of Lpin1, FKBP51 and S-adenosyl methionine decarboxylase was also abolished in the ADX mice. On the other hand, although the circadian expression of clock or clock-related genes, such as mPer2, DBP, E4BP4, mDec1, Usp2 and Wee1 remained almost totally intact in the liver of ADX mice, it was extremely damped in homozygous Clock mutant mice. The present findings suggested that one type of hepatic circadian genes in mice is transcriptionally regulated by core components of the circadian clock, such as CLOCK and BMAL1, and that the other depends on the adrenal gland.