A Role for SIRT2-Dependent Histone H3K18 Deacetylation in Bacterial Infection

摘要

Introduction:Posttranslational modification of histones is a well-documented mechanism by which the chromatin structure is modulated to regulate gene expression. Increasing evidence is revealing the strong impact of bacterial pathogens on host chromatin. However, our knowledge of the mechanisms underlying pathogen-induced chromatin changes and the impact of histone modifications and chromatin modifiers on infection is still in its infancy.Methods: We used the model bacterium Listeria monocytogenes and analyzed the mechanisms underlying a specific histone modification, deacetylation of histone H3 on lysine 18 (H3K18). Through immunoblotting, mass spectrometry, and chromatin immunoprecipitation, we studied how infection affected this modification, both in vitro and in vivo. We used a combination of chemical inhibitors, small interfering RNA (siRNA), and knockout mice to discover the key role of the host histone deacetylase sirtuin 2 (SIRT2) and determine its effect on infection. We performed microarray analysis to identify how infection and SIRT2 modulated host transcription.