Circadian succession of molecular processes in living tissues.

Circadian succession of molecular processes in living tissues.
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DOI:
10.1186/s12920-018-0325-2
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发表时间:
2018-02-13
影响因子:
2.7
通讯作者:
Ptitsyn A
Ptitsyn A
中科院分区:
医学3区
文献类型:
--
作者:
Fadda A;El Anbari M;Ptitsyn A

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不同起源、周期和幅度的振荡在细胞过程的调节中起着重要的作用。最广泛研究的是基因表达活性的昼夜或近似每日变化。基因表达的时间由内部分子钟控制,保持稳定的周期性表达。在这项研究中,我们将注意力转向广泛的周期性表达的基因,这些基因参与多种细胞功能,这些功能可能受或不受内在生物钟的直接控制。是否所有的分子功能都在表达的基因中表达?或者,不同的分子功能是否在不同的时间执行?在它们的日常活动中,分子过程和功能是否有一种连续的模式?为了回答这些问题,我们重新分析了一些可从公共来源获得的小鼠昼夜节律基因表达数据。这些数据代表代谢活性外周组织(白色脂肪组织、棕色脂肪组织、肝脏)的正常功能。我们采用了新的方法来估计相位分配的置信度,以确定同时达到峰值的同步基因组,而不管表达的幅度或绝对强度。每个同步组已被注释以识别基因本体(GO)术语和分子途径。我们的分析确定了不同组织中特定于一天中特定时间的分子功能。改进的数据挖掘方法允许在具有同步峰值表达时间的基因组中发现功能和生物学途径。特别是,能量代谢的氧化阶段、DNA修复、mRNA加工、脂质生物合成等功能在时间上是分开的。这种时间上的区室化对于理解细胞回路是重要的,并且可以用于优化药物或基因组药物干预的时间。本文的在线版本(10.1186/s12920-018-0325-2)包含补充材料,可供授权用户使用。
Oscillations of different origin, period and amplitude play an important role in the regulation of cellular processes. Most widely studied is the circadian or approximately daily variation in gene expression activity. Timing of gene expression is controlled by internal molecular clock keeping steady periodic expression. In this study, we shift attention towards a broad range of periodically expressed genes involved in multiple cellular functions which may or may not be under direct control of the intrinsic circadian clock. Are all molecular functions represented in expressed genes at all times? Alternatively, are different molecular functions performed at different times? Is there a pattern of succession for molecular processes and functions throughout their daily activity period? To answer these questions, we re-analyzed a number of mouse circadian gene expression data available from public sources. These data represent the normal function of metabolically active peripheral tissues (white adipose tissue, brown adipose tissue, liver). We applied novel methods for the estimation of confidence in phase assignment to identify groups of synchronous genes peaking at the same time regardless of the amplitude or the absolute intensity of expression. Each synchronous group has been annotated to identify Gene Ontology (GO) terms and molecular pathways. Our analysis identified molecular functions specific to a particular time of the day in different tissues. Improved methodology for datamining allowed for the discovery of functions and biological pathways in groups of genes with synchronized peak expression time. In particular, such functions as oxidative phase of energy metabolism, DNA repair, mRNA processing, lipid biosynthesis and others are separated in time. This timewise compartmentalization is important for understanding the cellular circuitry and can be used to optimize the time of intervention with drug or genome medication. The online version of this article (10.1186/s12920-018-0325-2) contains supplementary material, which is available to authorized users.
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