title: Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization.
abstract: Nucleoid-associated protein HU, a conserved protein across eubacteria is necessary for maintaining the nucleoid organization and global regulation of gene expression. Mycobacterium tuberculosis HU (MtHU) is distinct from the other orthologues having 114 amino acid long carboxyl terminal extensions with a high degree of sequence similarity to eukaryotic histones. In this study, we demonstrate that the DNA binding property of MtHU is regulated by posttranslational modifications akin to eukaryotic histones. MtHU purified from M. tuberculosis cells is found to be acetylated on multiple lysine residues unlike the E. coli expressed recombinant protein. Using coimmunoprecipitation assay, we identified Eis as one of the acetyl transferases that interacts with MtHU and modifies it. Although Eis is known to acetylate aminoglycosides, the kinetics of acetylation showed that its protein acetylation activity on MtHU is robust. In vitro Eis modified MtHU at various lysine residues, primarily those located at the carboxyl terminal domain. Acetylation of MtHU caused reduced DNA interaction and alteration in DNA compaction ability of the NAP. Over-expression of the Eis leads to hyperacetylation of HU and decompaction of genome. These results provide first insights into the modulation of the nucleoid structure by lysine acetylation in bacteria.
authors.affiliation: Department of Microbiology and Cell biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
authors.forename: Soumitra
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology and Cell biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Padmanabhan
authors.affiliation: Department of Microbiology and Cell biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
authors.forename: Chinmay
authors.initials: C
authors.lastname: Anand
authors.affiliation: Department of Microbiology and Cell biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India.|Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, 560064, India.
authors.forename: Valakunja
authors.initials: V
authors.lastname: Nagaraja
mesh_terms: D000107:Acetylation; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D016680:Genome, Bacterial; D008239:Lysine / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D014166:Transferases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; C040330:histone-like protein HU, bacteria; D014166:Transferases; D008239:Lysine