The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding

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-methy...

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Bibliographic Details
Published in:Nucleic acids research 2015-04, Vol.43 (8), p.3922-3937
Main Authors: Sharma, Garima, Upadhyay, Sandeep, Srilalitha, M, Nandicoori, Vinay K, Khosla, Sanjeev
Format: Article
Language:English
Subjects:
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Cell Line
Cell Nucleus - enzymology
Chromatin - metabolism
CpG Islands
DNA (Cytosine-5-)-Methyltransferases - chemistry
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA - metabolism
DNA Methylation
Gene regulation, Chromatin and Epigenetics
Histones - metabolism
Humans
Mycobacterium tuberculosis
Mycobacterium tuberculosis - enzymology
Phosphorylation
Protein Binding
Protein Processing, Post-Translational
Protein Sorting Signals
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkv261