Institut Pasteur, Unité Biologie des Bactéries Intracellulaires, Paris 75015, France.
Cell Host Microbe. 2013 Apr 17;13(4):395-405. doi: 10.1016/j.chom.2013.03.004.
Histone posttranslational modifications control eukaryotic gene expression and regulate many biological processes including immunity. Pathogens alter host epigenetic control to aid pathogenesis. We find that the intracellular bacterial pathogen Legionella pneumophila uses a Dot/Icm type IV secreted effector, RomA, to uniquely modify the host chromatin landscape. RomA, a SET domain-containing methyltransferase, trimethylates K14 of histone H3, a histone mark not previously described in mammals. RomA localizes to the infected cell nucleus where it promotes a burst of H3K14 methylation and consequently decreases H3K14 acetylation, an activating histone mark, to repress host gene expression. ChIP-seq analysis identified 4,870 H3K14 methylated promoter regions, including innate immune genes. Significantly reduced replication of a RomA-deleted strain in host cells was trans-complemented by wild-type, but not by catalytically inactive, RomA. Thus, a secreted L. pneumophila effector targets the host cell nucleus and modifies histones to repress gene expression and promote efficient intracellular replication.
组蛋白翻译后修饰控制真核基因表达，并调节包括免疫在内的许多生物学过程。病原体改变宿主的表观遗传控制以辅助发病机制。我们发现，细胞内细菌病原体军团菌利用一种 Dot/Icm 型 IV 分泌效应蛋白 RomA 来独特地修饰宿主染色质景观。RomA 是一种含有 SET 结构域的甲基转移酶，它将组蛋白 H3 的 K14 三甲基化，这是一种以前在哺乳动物中未被描述过的组蛋白标记。RomA 定位于感染细胞的细胞核内，在那里它促进 H3K14 甲基化的爆发，从而降低 H3K14 乙酰化，这是一种激活的组蛋白标记，从而抑制宿主基因表达。ChIP-seq 分析鉴定了 4870 个 H3K14 甲基化启动子区域，包括先天免疫基因。通过野生型 RomA 而不是无催化活性的 RomA 对 RomA 缺失株在宿主细胞中的复制减少进行了转互补。因此，一种分泌的 L. pneumophila 效应蛋白靶向宿主细胞核，并修饰组蛋白以抑制基因表达并促进有效的细胞内复制。
