Timing of circadian genes in mammalian tissues
Timing of circadian genes in mammalian tissues
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DOI：
10.1038/srep05782
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发表时间：
2014-07-22
影响因子：
4.6
通讯作者：
Herzel, Hanspeter
中科院分区：
文献类型：
--
作者：
Korencic, Anja;Kosir, Rok;Herzel, Hanspeter
生理时钟是生理上驱动日常节律的内源性振荡器。细胞自主时钟由一个互锁的转录反馈回路网络控制。数以百计的时钟控制基因（ccg）调节着组织的特定功能。转录组研究表明，不同器官（如肝脏、心脏、肾上腺）的CCGs具有显著不同的峰相分布。为了研究哺乳动物外周组织CCGs的相变异性，我们基于表达谱和已知的顺式调控位点建立了小鼠肝脏和肾上腺的核心时钟模型。与e -box、ROR-elements和d -box相关的“调制因子”可以解释ccg的可变节律，这被证明是细胞色素P450和12h谐波的差异调节。通过改变模型参数，我们探索如何产生组织特异性峰相分布。通过分析BMAL1和REV-ERB转录因子的ChIP-seq数据，证实了e -box和ror元件的核心作用。
Circadian clocks are endogenous oscillators driving daily rhythms in physiology. The cell-autonomous clock is governed by an interlocked network of transcriptional feedback loops. Hundreds of clock-controlled genes (CCGs) regulate tissue specific functions. Transcriptome studies reveal that different organs (e. g. liver, heart, adrenal gland) feature substantially varying sets of CCGs with different peak phase distributions. To study the phase variability of CCGs in mammalian peripheral tissues, we develop a core clock model for mouse liver and adrenal gland based on expression profiles and known cis-regulatory sites. 'Modulation factors' associated with E-boxes, ROR-elements, and D-boxes can explain variable rhythms of CCGs, which is demonstrated for differential regulation of cytochromes P450 and 12 h harmonics. By varying model parameters we explore how tissue-specific peak phase distributions can be generated. The central role of E-boxes and ROR-elements is confirmed by analysing ChIP-seq data of BMAL1 and REV-ERB transcription factors.