title: Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3.
abstract: Mycobacteria are successful pathogens that modulate the host immune response through unclear mechanisms. Here we show that Rv1988, a secreted mycobacterial protein, is a functional methyltransferase that localizes to the host nucleus and interacts with chromatin. Rv1988 methylates histone H3 at H3R42 and represses the genes involved in the first line of defence against mycobacteria. H3R42me2, a non-tail histone modification, is present at the entry and exit point of DNA in the nucleosome and not within the regulatory sites in the N-terminal tail. Rv1988 deletion in Mycobacterium tuberculosis reduces bacterial survival in the host, and experimental expression of M. tuberculosis Rv1988 in non-pathogenic Mycobacterium smegmatis negatively affects the health of infected mice. Thus, Rv1988 is an important mycobacterial virulence factor, which uses a non-canonical epigenetic mechanism to control host cell transcription.
authors.affiliation: CDFD, Nampally, Hyderabad 500001, India.|Graduate Studies, Manipal University, Manipal 576104, India.
authors.forename: Imtiyaz
authors.initials: I
authors.lastname: Yaseen
authors.affiliation: National Institute of Immunology, New Delhi 110067, India.
authors.forename: Prabhjot
authors.initials: P
authors.lastname: Kaur
authors.affiliation: National Institute of Immunology, New Delhi 110067, India.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Nandicoori
authors.affiliation: CDFD, Nampally, Hyderabad 500001, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Khosla
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic / Q000235:genetics*; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000382:microbiology; D013058:Mass Spectrometry; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000382:microbiology; D016297:Mutagenesis, Site-Directed; D009163:Mycobacterium bovis; D020102:Mycobacterium smegmatis / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001426:Bacterial Proteins; D006657:Histones; D001120:Arginine; D008780:Methyltransferases; C000607441:Rv1988 protein, Mycobacterium tuberculosis