Acetylation of lysine 182 inhibits the ability of <i>Mycobacterium tuberculosis</i> DosR to bind DNA and regulate gene expression during hypoxia Jing Bi Zongchao Gou Fengzhu Zhou Yiqing Chen Jianhua Gan Jun Liu Honghai Wang Xuelian Zhang 10.6084/m9.figshare.7937039.v1 https://tandf.figshare.com/articles/journal_contribution/Acetylation_of_lysine_182_inhibits_the_ability_of_i_Mycobacterium_tuberculosis_i_DosR_to_bind_DNA_and_regulate_gene_expression_during_hypoxia/7937039 <p>The DosR regulon is believed to be a key factor in latency adaptation of <i>Mycobacterium tuberculosis</i> and is strongly induced by multiple stresses, including hypoxia. Previous studies have revealed reversible acetylation of the conserved core DNA-binding lysine residue 182 (K182) of DosR in <i>M. tuberculosis</i>. In this study, we demonstrated that acetylated K182 plays an important role in the DNA-binding ability of DosR and that acetylation of K182 completely abolished the affinity of DosR for DNA in vitro. Antibodies that specifically recognized acetyllysine at position 182 of DosR were used to monitor DosR acetylation. We found that in vitro acetylation of K182 could be removed by deacetylase Rv1151c and that either the deacetylase<i>-</i>deletion strain ∆<i>npdA</i> or treatment with a deacetylase inhibitor resulted in increased levels of K182 acetylation in vivo. The physiological significance of DosR acetylation was demonstrated by decreased levels of acetylated K182 in <i>M. tuberculosis</i> in response to hypoxia and by the effects of K182 acetylation on the transcript levels of DosR regulon genes. Since the DosR regulon plays a critical role during host infection by <i>M. tuberculosis</i>, our findings suggest that targeting DosR acetylation may be a viable strategy for antituberculosis drug development.</p> 2019-04-02 08:38:11 specifically recognized acetyllysine regulate gene expression deletion strain ∆< lysine 182 inhibits revealed reversible acetylation k182 completely abolished dosr regulon plays dosr regulon genes deacetylase inhibitor resulted conserved core dna mycobacterium tuberculosis </ acetylated k182 plays monitor dosr acetylation dosr regulon tuberculosis </ acetylated k182 position 182 dosr acetylation npda </ k182 acetylation k182 could viable strategy transcript levels strongly induced previous studies physiological significance multiple stresses latency adaptation key factor increased levels important role host infection findings suggest decreased levels deacetylase rv1151c critical role bind dna