Identification and functional analysis of early gene expression induced by circadian light-resetting in Drosophila.
Identification and functional analysis of early gene expression induced by circadian light-resetting in Drosophila.
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DOI：
10.1186/s12864-015-1787-7
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发表时间：
2015-08-01
期刊：
影响因子：
4.4
通讯作者：
Tauber E
中科院分区：
文献类型：
--
作者：
Adewoye AB;Kyriacou CP;Tauber E
环境光暗周期是多细胞生物体维持24小时生物节律的主要线索。在果蝇中，光夹带是由光敏蛋白质光敏色素介导的，但双翅目生物钟的光重置中转录调控的作用和程度尚不清楚。鉴于广泛的转录变化，在响应光以前确定在哺乳动物中，我们试图分析光诱导的全球转录变化，在苍蝇的头部，通过使用Affytron微阵列。苍蝇进行了30分钟的光脉冲在夜间早些时候（3小时后熄灯），刺激，导致实质性的相位延迟的昼夜节律。然后，我们分析了光刺激后1小时基因表达的变化。我们确定了200个基因，它们的转录本在光脉冲的作用下发生了显着改变，错误发现率为10%。对这些基因及其生物学功能的分析表明，至少有六个生物过程参与了光诱导的节律性活动的延迟相移。这些过程包括信号传导、离子通道转运、受体活性、突触组织、信号转导和染色质重塑。使用RNAi，22个基因的表达在时钟神经元中下调，导致对昼夜节律输出的显著影响。例如，虽然连续光通常会导致野生型果蝇的节律性，但Kr-h1，Nipped-A，Thor，nrv 1，Nf 1，CG 11155（离子型谷氨酸受体）和Fmr 1的敲低导致果蝇的节律性，这表明光输入途径的时钟中断。我们的分析提供了第一个洞察早期响应基因，被激活的光和光重置的果蝇时钟的贡献。分析表明，多个域和途径，可能与光夹带，包括一个机制，是由一组光激活的染色质重塑基因。本文的在线版本（doi：10.1186/s12864-015-1787-7）包含补充材料，可供授权用户使用。
The environmental light–dark cycle is the dominant cue that maintains 24-h biological rhythms in multicellular organisms. In Drosophila, light entrainment is mediated by the photosensitive protein CRYPTOCHROME, but the role and extent of transcription regulation in light resetting of the dipteran clock is yet unknown. Given the broad transcriptional changes in response to light previously identified in mammals, we have sought to analyse light-induced global transcriptional changes in the fly’s head by using Affymetrix microarrays. Flies were subjected to a 30-min light pulse during the early night (3 h after lights-off), a stimulus which causes a substantial phase delay of the circadian rhythm. We then analysed changes in gene expression 1 h after the light stimulus. We identified 200 genes whose transcripts were significantly altered in response to the light pulse at a false discovery rate cut-off of 10 %. Analysis of these genes and their biological functions suggests the involvement of at least six biological processes in light-induced delay phase shifts of rhythmic activities. These processes include signalling, ion channel transport, receptor activity, synaptic organisation, signal transduction, and chromatin remodelling. Using RNAi, the expression of 22 genes was downregulated in the clock neurons, leading to significant effects on circadian output. For example, while continuous light normally causes arrhythmicity in wild-type flies, the knockdown of Kr-h1, Nipped-A, Thor, nrv1, Nf1, CG11155 (ionotropic glutamate receptor), and Fmr1 resulted in flies that were rhythmic, suggesting a disruption in the light input pathway to the clock. Our analysis provides a first insight into the early responsive genes that are activated by light and their contribution to light resetting of the Drosophila clock. The analysis suggests multiple domains and pathways that might be associated with light entrainment, including a mechanism that was represented by a light-activated set of chromatin remodelling genes. The online version of this article (doi:10.1186/s12864-015-1787-7) contains supplementary material, which is available to authorized users.