Hogenesch John B, Panda Satchidananda, Kay Steve, Takahashi Joseph S
The Genomics Institute, Novartis Research Foundation, San Diego, CA 9212, USA.
Novartis Found Symp. 2003;253:171-80; discussion 52-5, 102-9, 180-3 passim.
Circadian oscillators orchestrate daily rhythms in behaviour and physiology to adapt to the predictable daily appearance of light. Identifying the complement of circadian-regulated transcripts in major organs is critical in the understanding of both the biochemical targets of clock regulation and the mechanism of such control. Recent analysis of temporal gene expression patterns in peripheral and central oscillators have revealed hundreds of circadian-regulated transcripts, most of which are tissue-specific. Mapping of these transcripts to physiological processes and pathways has revealed that major functions of those organs tested are under circadian regulation, and importantly, key and rate-limiting steps in these processes are often the targets of circadian control. Overall, nearly 100% of the mammalian genome may be regulated by the clock, demonstrating the pervasive control of the circadian oscillator in temporal coordination of transcription throughout the organism. This wealth of circadian outputs offers exciting challenges to deciphering systems-level transcriptional regulatory mechanisms that underlie spatiotemporal gene expression.
昼夜节律振荡器协调行为和生理的每日节律，以适应光的可预测的每日出现。确定主要器官中昼夜节律调节转录本的互补物对于理解时钟调节的生化靶点和这种控制机制至关重要。最近对外周和中枢振荡器中时间基因表达模式的分析揭示了数百种昼夜节律调节的转录本，其中大多数是组织特异性的。将这些转录本映射到生理过程和途径表明，所测试的那些器官的主要功能受昼夜节律调节，重要的是，这些过程中的关键和限速步骤通常是昼夜节律控制的靶点。总体而言，近100%的哺乳动物基因组可能受时钟调节，这表明昼夜节律振荡器在整个生物体转录的时间协调中具有普遍控制作用。这些丰富的昼夜节律输出为破译时空基因表达背后的系统水平转录调节机制带来了令人兴奋的挑战。
