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PNAS:睡眠周期紊乱改变基因表达的周期性

来源:生物谷 2014-01-23 21:33

近日,英国Surrey大学研究人员发现,睡眠模式的改变(如切换到夜班工作)可以显著影响基因表达。相关研究发表在PNAS,研究小组描述了他们对志愿者进行的一项睡眠研究,他们发现睡眠模式的改变显著影响基因的表达。

科学家们知道,我们的基因负责创建蛋白质和我们机体发挥各种作用所需要的其他化学物质。基因表达是周期性的,有时表达多,有时表达少,取决于一天中的时间。但目前不知道的是,当这些内部循环被打乱时会发生什么。

此外,大多数人都知道,他们的身体运行有一个内部生物钟,这可以让他们知道什么时候吃饭,睡觉。

但是不清除的是当我们破坏那些活动之一,特别是睡觉的时候,我们的内部生物钟会发生什么。为了了解更多信息,研究人员邀请22名青年志愿者协助参与研究,他们各自同意在研究中心睡三天,他们的昼/夜生物钟被调整修改。

研究人员还在整个研究过程中采取了血样,以测试昼/夜生物钟改变对基因表达产生的影响,研究小组发现,志愿者的1,396个基因中40个基因活性表达的时间发生改变。他们还发现,常量表达的180个基因,突然变得“飘忽不定”(表达没有规律性)。

该小组的研究表明,经历时差的人(飞往遥远的地方)或上夜班,其基因表达的周期性会发生“深刻的中断”。研究人员补充说,他们的发现可能解释为什么人们会抱怨各种各样的问题,当他们的睡眠周期被打乱时。

如果他们留在一个地方很久,大多数经历时差后的人最终会恢复正常,这表明生物钟的改变对基因表达的影响是暂时的,但仍然是不明确的,是否所有受影响的基因都会恢复正常。(生物谷Bioon.com)


 

Mistimed sleep disrupts circadian regulation of the human transcriptome

Simon N. Archer,et al.

Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep–wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep–wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep–wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.

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