© The Author 2005. Kazusa DNA Research Institute
Genome-wide Expression Analysis Reveals 100 Adrenal Gland-dependent Circadian Genes in the Mouse Liver
1Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST) Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
2Graduate School of Life and Environmental Sciences, University of Tsukuba Tsukuba, Ibaraki 305-8502, Japan
3Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology Aomi Frontier Bldg 17F, 2-43 Aomi, Koto-Ku, Tokyo 135-0064, Japan
4Transcriptome Research Center, National Institute of Radiological Sciences (NIRS) 4-9-1 Anagawa, Chiba, Chiba 263-8555, Japan
5Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University 1091-1 Suarashi, Sagamiko, Tsukui, Kanagawa 199-0195, Japan
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.
Key words: circadian rhythm; glucocorticoids; Clock; DNA microarray; liver
*To whom correspondence should be addressed. Tel. +81-29-861-6053, Fax. +81-29-861-9499, E-mail: n.ishida{at}aist.go.jp
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