title: The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding.
abstract: To effectively modulate the gene expression within an infected mammalian cell, the pathogen Mycobacterium tuberculosis would need to bring about epigenetic modifications at appropriate genomic loci. Working on this hypothesis, we show in this study that the mycobacterial protein Rv2966c is a 5-methylcytosine-specific DNA methyltransferase that is secreted out from the mycobacterium and gets localized to the nucleus in addition to the cytoplasm inside the host cell. Importantly, Rv2966c binds to specific DNA sequences, methylates cytosines predominantly in a non-CpG context and its methylation activity is positively influenced by phosphorylation. Interestingly, like the mammalian DNA methyltransferase, DNMT3L, Rv2966c can also interact with histone proteins. Ours is the first study that identifies a protein from a pathogenic bacteria with potential to influence host DNA methylation in a non-canonical manner providing the pathogen with a novel mechanism to alter the host epigenetic machinery. This contention is supported by repression of host genes upon M. tuberculosis infection correlated with Rv2966c binding and non-CpG methylation.
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India Graduate Studies, Manipal University, Manipal 576104, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Sharma
authors.affiliation: National Institute of Immunology, Delhi 110067, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Upadhyay
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India.
authors.forename: M
authors.initials: M
authors.lastname: Srilalitha
authors.affiliation: National Institute of Immunology, Delhi 110067, India.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Nandicoori
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India sanjuk@cdfd.org.in.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Khosla
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000378:metabolism*; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals
chemical_list: D001426:Bacterial Proteins; D002843:Chromatin; D006657:Histones; D021382:Protein Sorting Signals; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases
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