Transcriptional oscillation of canonical clock genes in mouse peripheral tissues
Transcriptional oscillation of canonical clock genes in mouse peripheral tissues
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DOI：
10.1186/1471-2199-5-18
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发表时间：
2004-10-09
影响因子：
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通讯作者：
Takumi, T
中科院分区：
文献类型：
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作者：
Yamamoto, T;Nakahata, Y;Takumi, T
背景资料：大约24小时的昼夜节律是在从原核生物到人类的几乎所有生物体中观察到的基本生理功能。生物钟基因的发现使我们能够研究昼夜节律行为和时间生理过程（如激素分泌）的分子基础，并促使人们认为分子钟不仅存在于哺乳动物下丘脑的中央起搏器-视交叉上核（SCN）中，而且存在于外周组织，甚至永生细胞中。此外，以前的分子解剖表明，在分子水平上的昼夜节律振荡的机制是基于时钟和时钟控制的基因的转录调控。结果：我们系统地分析了时钟和时钟控制的基因在小鼠外周组织的mRNA表达。8个基因（mBmal 1、mNpas 2、mRev-erbalpha、mDbp、mRev-erbbeta、mPer 3、mPer 1和mPer 2;以节律峰的时间顺序给出）在除睾丸外的所有组织中显示出稳健的mRNA昼夜表达，表明这些基因是分子生物钟的核心分子。生物信息学分析表明，这些基因具有一个或三个转录因子的组合（RORE，DBPE，和E-box），它们在人类，小鼠和大鼠基因组序列中是保守的，并且表明这3个元件可能负责典型时钟基因表达的生物学定时。对经典生物钟基因振荡谱的观察不仅有助于生理和病理学研究生物钟在不同器官中的作用，而且对于系统地理解生物钟的转录调控也具有重要意义在基因组的基础上。我们发现的典型时钟基因的振荡表达与时间顺序为我们提供了一个有趣的假设，即所有的时钟和时钟控制的基因的周期性定时可能依赖于几个转录元件，包括3个已知的元件，E-box，RORE，和DBPE。
Background: The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes.Results: We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbalpha, mDbp, mRev-erbbeta, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box), which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes.Conclusions: The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements including 3 known elements, E-box, RORE, and DBPE.