biostudies-literatureLiu YChina Agriculture Research System of MOF and MARANational Natural Science Foundation of China1645-1660https://www.ebi.ac.uk/biostudies/studies/S-EPMC10899749biostudies-literatureUnknown52(4)H-NS, the histone-like nucleoid-structuring protein in bacteria, regulates the stability of the bacterial genome by inhibiting the transcription of horizontally transferred genes, such as the type III and type VI secretion systems (T3/T6SS). While eukaryotic histone posttranslational modifications (PTMs) have been extensively studied, little is known about prokaryotic H-NS PTMs. Here, we report that the acetylation of H-NS attenuates its ability to silence horizontally transferred genes in response to amino acid nutrition and immune metabolites. Moreover, LC-MS/MS profiling showed that the acetyllysine sites of H-NS and K120 are indispensable for its DNA-binding ability. Acetylation of K120 leads to a low binding affinity for DNA and enhances T3/T6SS expression. Furthermore, acetylation ofNucleic acids researchLysine acetylation regulates the AT-rich DNA possession ability of H-NS.PMC10899749CARS-473200243632130108Zhou MLiu YBu YQin LWang QZhang YShao SfalseLysine acetylation regulates the AT-rich DNA possession ability of H-NS.H-NS, the histone-like nucleoid-structuring protein in bacteria, regulates the stability of the bacterial genome by inhibiting the transcription of horizontally transferred genes, such as the type III and type VI secretion systems (T3/T6SS). While eukaryotic histone posttranslational modifications (PTMs) have been extensively studied, little is known about prokaryotic H-NS PTMs. Here, we report that the acetylation of H-NS attenuates its ability to silence horizontally transferred genes in response to amino acid nutrition and immune metabolites. Moreover, LC-MS/MS profiling showed that the acetyllysine sites of H-NS and K120 are indispensable for its DNA-binding ability. Acetylation of K120 leads to a low binding affinity for DNA and enhances T3/T6SS expression. Furthermore, acetylation of2024-01-01T00:00:00Z2024 Feb2025-05-18T12:53:33.76Z2025-05-18T12:53:33.76ZS-EPMC108997493805936610.1093/nar/gkad1172