Cytosolic PRRs are required to upregulate inflammatory gene expression upon EZH2 inhibition with GSK343

EZH2 is a histone methyltransferase that deposits the repressive histone H3 lysine 27 trimethylation (H3K27me3). This mark has been reported to silence expression of various repetitive elements in the genome. We sought to identify the effect of EZH2 inhibition on coding and non-coding, repetitive RNA expression. We generated a novel mutant mouse line whose ability to detect induced repeat element expression has been abrogated. We report that the mutant splenic B cells fail to upregulate inflammatory gene expression upon EZH2 inhibition, despite comparable upregulation of various repetitive elements with WT. Coding and non-coding repetitive RNA expression profiles of WT and triple mutant splenocytes upon GSK343 treatment

EZH2是一种组蛋白甲基转移酶（histone methyltransferase），可催化生成具有转录抑制作用的组蛋白H3赖氨酸27三甲基化修饰（H3K27me3）。该修饰已被报道可沉默基因组中各类重复序列元件的表达。本研究旨在明确EZH2抑制对编码型与非编码型重复RNA表达的调控效应。我们构建了一株新型突变小鼠品系，其检测诱导型重复序列元件表达的功能已丧失。研究结果显示，尽管突变型小鼠的脾脏B细胞与野生型（wild type, WT）小鼠一样可上调多种重复序列元件的表达，但在EZH2被抑制后，其无法上调炎症相关基因的表达。野生型与三突变型脾细胞在GSK343处理后的编码及非编码重复RNA表达谱