炎症体
EZH2型
细胞生物学
抄写(语言学)
染色质
生物
曲古抑菌素A
组蛋白脱乙酰基酶
转录因子
乙酰化
甲基转移酶
癌症研究
组蛋白
化学
甲基化
生物化学
基因
受体
语言学
哲学
作者
Yuan Jia,Qingchen Zhu,Xingli Zhang,Zhenzhen Wen,Guiheng Zhang,Ni Li,Yanbo Pei,Yan Wang,Siyu Pei,Jing Xu,Pan Jia,Chao Peng,Wei Lu,Jun Qin,Qian Cao,Yichuan Xiao
标识
DOI:10.1038/s41418-022-00992-3
摘要
Inflammasome contributes to the pathogenesis of various inflammatory diseases, but the epigenetic mechanism controlling its activation remains elusive. Here, we found that the histone methyltransferase Ezh2 mediates the activation of multiple types of inflammasomes in macrophages/microglia independent of its methyltransferase activity and thus promotes inflammasome-related pathologies. Mechanistically, Ezh2 functions through its SANT2 domain to maintain the enrichment of H3K27 acetylation in the promoter region of the long noncoding RNA (lncRNA) Neat1, thereby promoting chromatin accessibility and facilitating p65-mediated transcription of Neat1, which is a critical mediator of inflammasome assembly and activation. In addition, the tumour suppressor protein p53 competes with Ezh2 for the same binding region in the Neat1 promoter and thus antagonises Ezh2-induced Neat1 transcription and inflammasome activation. Therefore, loss of Ezh2 strongly promotes the binding of p53, which recruits the deacetylase SIRT1 for H3K27 deacetylation of the Neat1 promoter and thus suppresses Neat1 transcription and inflammasome activation. Overall, our study demonstrates an epigenetic mechanism involved in modulating inflammasome activation through an Ezh2/p53 competition model and highlights a novel function of Ezh2 in maintaining H3K27 acetylation to support lncRNA Neat1 transcription.
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