Lysine acetylation regulates the AT-rich DNA possession ability of H-NS

Abstract

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 of K120 impairs the AT-rich DNA recognition ability of H-NS. In addition, lysine acetylation in H-NS modulates in vivo bacterial virulence. These findings reveal the mechanism underlying H-NS PTMs and propose a novel mechanism by which bacteria counteract the xenogeneic silencing of H-NS.

Bacterial chromatin proteins, transcription, and DNA topology: Inseparable partners in the control of gene expression

“…Acetylation of the Lys19 residue of the oligomerization domain may lead to enhanced effective repression of glutamine synthetase genes by H-NS (Liu, Li, et al, 2023). Conversely, acetylation of a Lys120 residue in the DNA-binding domain of H-NS may lead to weaker DNA-binding affinity and a subsequent increase in gene expression (Liu, Zhou, et al, 2023) Peng & Weber, 2019). A well-studied condensate of Dps provides an interesting example.…”