Mitochondrial stress induces chromatin reorganization to promote longevity and UPRmt

Organisms respond to mitochondrial stress through the upregulation of an array of protective genes, often perpetuating an early response to metabolic dysfunction across a lifetime. We find that mitochondrial stress causes widespread changes in chromatin structure through histone H3K9 di-methylation marks traditionally associated with gene silencing. Mitochondrial stress response activation requires the di-methylation of histone H3K9 through the activity of the histone methyltransferase met-2 and the nuclear co-factor lin-65. While globally the chromatin becomes silenced by these marks, remaining portions of the chromatin open up, at which point the binding of canonical stress responsive factors such as DVE-1 occurs. Thus, a metabolic stress response is established and propagated into adulthood of animals through specific epigenetic modifications that allow for selective gene expression and lifespan extension. comparison of gene expression changes in response to cco-1 RNAi treatment in N2, lin-65(n3441) and met-2(ok2307) populations of C. elegans L4 animals

生物体可通过上调一系列保护性基因以应对线粒体应激，该过程往往会使机体在整个生命周期中持续维持针对代谢功能障碍的早期应答。线粒体应激可通过传统上与基因沉默相关的组蛋白H3K9二甲基化（histone H3K9 di-methylation）标记，引发染色质结构的广泛重塑。线粒体应激应答的激活，需依赖组蛋白甲基转移酶（histone methyltransferase）MET-2与核辅因子LIN-65的协同作用，完成组蛋白H3K9的二甲基化修饰。尽管整体染色质会因此类标记而发生沉默，但仍有部分染色质区域发生开放，此时包括DVE-1在内的经典应激应答因子即可与之结合。由此，机体可通过特异性表观遗传修饰建立代谢应激应答，并将其传递至动物成年阶段，最终实现选择性基因表达与寿命延长。本数据集针对秀丽隐杆线虫（C. elegans）L4期幼虫的N2、lin-65(n3441)及met-2(ok2307)种群，比较其经cco-1 RNA干扰（RNAi）处理后的基因表达变化情况。