KAT2A和KAT2B是高表达于肠上皮的同源基因，但它们的功能尚不明确。本研究通过在小鼠肠上皮中双重敲除Kat2基因，发现此举导致幸存不下，且干扰素信号通路的激活现象和与干扰素相关的表型，包括肠干细胞的丧失。药理学试剂和无菌器官培养证实了干细胞内双链RNA触发干扰素信号通路的细胞内特异性。我们采用乙酰-蛋白质组学和dsRIP-seq技术研究了此反应的机制，发现线粒体编码的双链RNA是内在干扰素信号的来源。因此，Kat2a和Kat2b在调控线粒体功能以及维持肠道健康方面起着至关重要的作用。 在小鼠肠上皮中敲除Kat2a和Kat2b导致干扰素信号通路的激活 Kat2a/Kat2b敲除导致肠干细胞丢失和其他与干扰素激活一致的粘膜表型 组蛋白修饰质谱分析首次在体展示了Kat2a和Kat2b双敲除导致H3K9ac特异丧失，但与干扰素信号通路基因无相关性 全面蛋白质组学分析在小鼠肠道中确定了KAT2非组蛋白乙酰化靶点，包括线粒体蛋白 Kat2丧失会损害线粒体功能 dsRIP-seq鉴定了线粒体双链RNA作为Kat2双敲除时内在免疫反应的触发物。

Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in robust activation of interferon signaling and interferon-associated phenotypes including the loss of intestinal stem cells. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and dsRIP-seq were employed to interrogate the mechanism behind this response, which identified mitochondria-encoded double-stranded RNA as the source of intrinsic interferon signaling. Kat2a and Kat2b therefore play an essential role in regulating mitochondrial functions as well as maintaining intestinal health.Kat2a and Kat2b double knockout in the murine intestinal epithelium triggers activation of the interferon signaling pathway Kat2a/Kat2b knockout leads to intestinal stem cell loss and other mucosal phenotypes consistent with interferon activation Histone PTM mass spec profiling reveals the first in vivo study showing H3K9ac-specific loss with Kat2a and Kat2b double knockout, yet without correlation to interferon signaling pathway genes Comprehensive proteomic analysis identifies non-histone acetyl-lysine targets of KAT2 in the mouse intestine in vivo, including mitochondrial proteins Mitochondrial function is compromised upon Kat2 loss dsRIP-seq identifies double-stranded RNA from the mitochondria as a trigger for the intrinsic immune response upon Kat2 double knockout.