Abstract：
In mammals, intrinsic 24 h or circadian rhythms are primarily generated by the suprachiasmatic nuclei (SCN). Rhythmic daily changes in the transcriptome and proteome of SCN cells are controlled by interlocking transcription-translation feedback loops (TTFLs) of core clock genes and their proteins. SCN cells function as autonomous circadian oscillators, which synchronize through intercellular neuropeptide signalling. Physiological and behavioural rhythms can be severely disrupted by genetic modification of a diverse range of genes and proteins in the SCN. With the advent of next generation sequencing, there is unprecedented information on the molecular profile of the SCN and how it is affected by genetically targeted alteration. However, whether the expression of some genes is more readily affected by genetic alteration of the SCN is unclear. Here, using publicly available datasets from recent RNA-seq assessments of the SCN from genetically altered and control mice, we evaluated whether there are commonalities in transcriptome dysregulation. This was completed for four different phases across the 24 h cycle and was augmented by Gene Ontology Molecular Function (GO:MF) and promoter analysis. Common differentially expressed genes (DEGs) and/or enriched GO:MF terms included signalling molecules, their receptors, and core clock components. Finally, examination of the JASPAR database indicated that E-box and CRE elements in the promoter regions of several commonly dysregulated genes. From this analysis, we identify differential expression of genes coding for molecules involved in SCN intra- and intercellular signalling as a potential cause of abnormal circadian rhythms.
摘要：
在哺乳动物中,固有的24小时或昼夜节律主要由视交叉上核（SCN）产生。SCN细胞的转录组和蛋白质组的节律性每日变化受核心时钟基因及其蛋白质的互锁转录-翻译反馈环（TTFL）控制。SCN细胞作为自主昼夜节律振荡器，通过细胞间神经肽信号同步。通过对SCN中的各种基因和蛋白质进行遗传修饰，可以严重破坏生理和行为节律。随着下一代测序的出现，关于SCN的分子谱以及它如何受到遗传靶向改变的影响的信息是前所未有的。然而,某些基因的表达是否更容易受到SCN遗传改变的影响尚不清楚。这里,使用来自遗传改变和对照小鼠的SCN的最新RNA-seq评估的公开数据集，我们评估了转录组失调是否存在共性.这在24小时周期的四个不同阶段完成，并通过基因本体论分子功能（GO：MF）和启动子分析得到增强。常见的差异表达基因（DEGs）和/或富集的GO：MF术语包括信号分子，它们的受体，和核心时钟组件。最后,对JASPAR数据库的检查表明，几种常见失调基因的启动子区域中有E-box和CRE元件。从这个分析,我们确定了编码参与SCN细胞内和细胞间信号传导的分子的基因的差异表达是异常昼夜节律的潜在原因。
