Effect of neuron-specific short-form ATF6 overexpression on gene expression in the mouse brain

One major component of cellular proteome resides in the endoplasmic reticulum (ER), the key organelle for protein biogenesis in the secretory pathway. Disruption of ER proteostasis leads to ER stress, which subsequently activates multiple adaptive stress response pathways, collectedly termed as the unfolded protein response (UPR). One UPR branch is mediated by ATF6 (activating transcription factor 6). Activation of the ATF6 branch generates a transcriptional factor: short form ATF6 (sATF6). Since activation of this UPR branch has been shown to be neuroprotective in brain ischemia/stroke, it is critical to identify what genes are regulated by the sATF6 in neurons in vivo and determine the molecular mechanisms underlying the beneficial effects exerted by this UPR branch. In this study, we performed RNA-Seq analysis on the hippocampus from sATF6 conditional transgenic mice. Overall design: Compare gene expression between control (Emx-Cre) mice and sATF6 conditional knock-in (sATF6-KI; Rosa26-sATF6-MER;Emx1-Cre ) mice (n =3).

细胞蛋白质组的重要组分定位于内质网（endoplasmic reticulum, ER）——分泌通路中蛋白质生物合成的关键细胞器。内质网蛋白质稳态失衡会引发内质网应激，继而激活多种适应性应激应答通路，这些通路统称为未折叠蛋白反应（unfolded protein response, UPR）。UPR的一个分支由激活转录因子6（activating transcription factor 6, ATF6）介导。ATF6分支激活后会产生一种转录因子：截短型ATF6（short form ATF6, sATF6）。鉴于已有研究表明该UPR分支的激活在脑缺血/脑卒中中具有神经保护作用，因此明确体内神经元中sATF6调控的靶基因，并解析该UPR分支发挥有益作用的分子机制，具有重要研究价值。本研究针对sATF6条件性转基因小鼠的海马组织开展了RNA测序（RNA-Seq）分析。实验整体设计：对比对照组（Emx-Cre）小鼠与sATF6条件性敲入（sATF6-KI; Rosa26-sATF6-MER; Emx1-Cre）小鼠的基因表达水平（每组n=3）。