Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection.
A mammalian cell utilizes DNA methylation to modulate gene expression in response to environmental changes during development and differentiation. Aberrant DNA methylation changes as a correlate to diseased states like cancer, neurodegenerative conditions and cardiovascular diseases have been documented. Here we show genome-wide DNA methylation changes in macrophages infected with the pathogen M. tuberculosis. Majority of the affected genomic loci were hypermethylated in M. tuberculosis infected THP1 macrophages. Hotspots of differential DNA methylation were enriched in genes involved in immune response and chromatin reorganization. Importantly, DNA methylation changes were observed predominantly for cytosines present in non-CpG dinucleotide context. This observation was consistent with our previous finding that the mycobacterial DNA methyltransferase, Rv2966c, targets non-CpG dinucleotides in the host DNA during M. tuberculosis infection and reiterates the hypothesis that pathogenic bacteria use non-canonical epigenetic strategies during infection.
Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India.|Graduate Studies, Manipal University, Manipal 576104, India.
Garima
G
Sharma
Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
Divya Tej
DT
Sowpati
Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India.
Prakruti
P
Singh
National Institute of Immunology, Delhi 110067, India.
Mehak Zahoor
MZ
Khan
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Telangana State, India.
Rakesh
R
Ganji
National Institute of Immunology, Delhi 110067, India.
Sandeep
S
Upadhyay
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Telangana State, India.
Sharmistha
S
Banerjee
National Institute of Immunology, Delhi 110067, India.
Vinay Kumar
VK
Nandicoori
Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500001, India.
Sanjeev
S
Khosla
D001426:Bacterial Proteins / Q000378:metabolism*; D002874:Chromosome Mapping; D018899:CpG Islands; D003596:Cytosine / Q000737:chemistry; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007109:Immunity; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D000074084:THP-1 Cells; D014376:Tuberculosis / Q000235:genetics*
D001426:Bacterial Proteins; D006657:Histones; C510666:HupB protein, Mycobacterium tuberculosis; D003596:Cytosine