A novel mode of histone-like protein HupB regulating cell division through lysine acetylation.

HU, a small, basic histone-like protein, binds to bacterial genomic DNA, influencing DNA conformation, replication, and transcription. Its acetylation is a key post-translational modification affecting its DNA-binding activity. The role of HU acetylation in regulating cell division through the cell cycle regulatory system remained largely unknown. In this study, we find that stimulation of lysine acetylation or non-acetylation in HupB, a homolog of HU, differentially regulates the expression of cell cycle regulators, as well as cell growth and division in . Lys3, Lys13, and Lys83 in HupB were identified as acetylated residues by mass spectrometry. Mutating these residues to arginine (stimulating non-acetylation) in HupB impedes normal cell division, while substituting them with glycine (mimicking acetylation) allows for rapid cell duplication. The mimicry of non-acetylated HupB leads to enlarged abnormal cells, while stimulating acetylated HupB only reduces cell length. Transcription activation was observed in the mutant cells. Cell cycle regulators such as CtrA, GcrA and DnaA were differentially expressed in the mutants. HupB substitutions differentially bound to these cell cycle regulatory genes. These findings suggest that the appropriate acetylation of HupB regulates the expression of cell cycle regulators, thereby controlling cell division.