抄録
Recent studies of clock genes have revealed that an autoregulatory transcriptional feedback loop forms the core circadian rhythm generating mechanism in mammals. 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. The question arising from these findings is how the oscillatory expression of only a few canonical clock genes regulates the oscillation of a vast number of clock-controlled output genes. To elucidate the circadian regulation of gene expression in the liver, we used the DNA microarray chip technology. In the present talk, I show three possible mechanisms, the direct action of CLOCK/BMAL1 heterodimer on circadian gene expression, the indirect action of CLOCK/BMAL1 complex through the transactivation of other transcription factors, and the indirect action of clock molecules through the circadian production/secretion of humoral signals that can affect gene expression in peripheral tissues. Clock molecules work not only for the rhythm generation but also for the homeostatic regulation of various physiological functions. I will also talk about our recent studies that show the relationship between clock genes and metabolic diseases such as diabetes and obesity. [Jpn J Physiol 55 Suppl:S26 (2005)]
