Bar Ilan University Faculty of Medicine, Hanrietta Sold 8, Safed, 13215, Israel.
Sci Rep. 2018 Apr 20;8(1):6339. doi: 10.1038/s41598-018-24544-3.
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.
虽然已经研究了个体转录因子和顺式作用位点与精神疾病的关系，但对于反式作用因子和顺式作用因子对大脑基因转录的相对贡献知之甚少。我们使用来自两个进化上不同的小鼠品系的杂交小鼠进行 RNA-seq 分析，确定了顺式和反式因子对前额叶皮层和杏仁核中基因表达的贡献，这两个脑区与应激反应有关，以及慢性社交挫败（CSD）后前额叶皮层中顺式和反式因子的贡献在小鼠中。更多的基因受到两个脑区顺式调控因子的调控，这表明顺式基因调控在大脑中的重要性。然而，与前额叶皮层相比，杏仁核中受反式调控机制调控的基因增加。这些基因参与突触功能，并且富含转录因子（包括 Egr1）结合位点。CSD 诱导前额叶皮层中受反式调控机制调控的基因增加，并诱导出与未受应激的杏仁核相似的模式。总的来说，我们展示了大脑中顺式和反式调控机制的特定部位模式，并表明这些模式可以被心理触发所改变。
