While both individual transcription factors and cis-acting sites have been studied in relation to psychiatric disorders, there is little knowledge of the relative contribution of trans-acting and cis-acting factors to gene transcription in the brain. Using an RNA-seq approach in mice bred from two evolutionary-distinct mice strains, we determined the contribution of cis and trans factors to gene expression in the prefrontal cortex and amygdala, two regions of the brain relevant to the stress response, and the contribution of cis and trans factors in the prefrontal cortex after Chronic Social Defeat (CSD) in mice. More genes were regulated by cis-regulatory factors in both brain regions, underlying the importance of cis-acting gene regulation in the brain. However, there was an increase in genes regulated by trans-regulatory mechanisms in the amygdala, compared to the prefrontal cortex. These genes were involved in synaptic functions, and were enriched for binding sites for transcription factors, including Egr1. CSD induced an increase in genes regulated by trans-regulatory mechanisms in the prefrontal cortex, and induced a pattern similar to the unstressed amygdala. Overall, we show brain site-specific patterns in cis and trans regulatory mechanisms, and show that these patterns can be modified by a psychological trigger.

中文翻译：

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杏仁核和前额叶皮层中顺式和反式基因转录调控机制的不同贡献以及社会压力的调节。

尽管已经研究了与精神病有关的个体转录因子和顺式作用位点，但对反式和顺式作用因子对大脑基因转录的相对贡献了解甚少。使用RNA-seq方法在由两种进化不同的小鼠品系繁殖的小鼠中，我们确定了顺式和反式因子对前额叶皮层和杏仁核这两个与压力反应相关的大脑区域的基因表达的贡献以及其贡献慢性社交挫败（CSD）后小鼠前额叶皮层的顺式和反式因子的变化 在两个大脑区域中，更多的基因受到顺式调节因子的调节，这说明了顺式作用基因在大脑中调节的重要性。然而，与前额叶皮层相比，杏仁核中受反式调节机制调节的基因增加了。这些基因参与突触功能，并丰富了转录因子（包括Egr1）的结合位点。CSD诱导了前额叶皮层中由反式调节机制调节的基因的增加，并诱导了与未受力的杏仁核相似的模式。总体而言，我们在顺式和反式调节机制中显示了大脑特定于位点的模式，并表明可以通过心理触发来修改这些模式。并诱导出与未受力的杏仁核相似的模式。总体而言，我们在顺式和反式调节机制中显示了大脑特定于位点的模式，并表明可以通过心理触发来修改这些模式。并诱导出与未受力的杏仁核相似的模式。总体而言，我们在顺式和反式调节机制中显示了大脑特定于位点的模式，并表明可以通过心理触发来修改这些模式。