Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France.
Science. 2013 Aug 2;341(6145):1238858. doi: 10.1126/science.1238858.
Pathogens dramatically affect host cell transcription programs for their own profit during infection, but in most cases, the underlying mechanisms remain elusive. We found that during infection with the bacterium Listeria monocytogenes, the host deacetylase sirtuin 2 (SIRT2) translocates to the nucleus, in a manner dependent on the bacterial factor InlB. SIRT2 associates with the transcription start site of a subset of genes repressed during infection and deacetylates histone H3 on lysine 18 (H3K18). Infecting cells in which SIRT2 activity was blocked or using SIRT2(-/-) mice resulted in a significant impairment of bacterial infection. Thus, SIRT2-mediated H3K18 deacetylation plays a critical role during infection, which reveals an epigenetic mechanism imposed by a pathogenic bacterium to reprogram its host.
病原体在感染过程中为了自身利益会显著影响宿主细胞的转录程序,但在大多数情况下,其潜在机制仍难以捉摸。我们发现,在感染细菌李斯特菌(Listeria monocytogenes)时,宿主去乙酰化酶 SIRT2(sirtuin 2)会依赖于细菌因子 InlB 而转位到细胞核中。SIRT2 与感染过程中受抑制的一组基因的转录起始位点结合,并使组蛋白 H3 赖氨酸 18(H3K18)去乙酰化。阻断 SIRT2 活性或使用 SIRT2(-/-) 小鼠感染细胞,会导致细菌感染显著受损。因此,SIRT2 介导的 H3K18 去乙酰化在感染过程中发挥着关键作用,这揭示了一种由致病菌施加的表观遗传机制,以重新编程其宿主。