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Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection.

ABSTRACT: 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.

SUBMITTER: Sharma G

PROVIDER: S-EPMC4845000 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection.

Sharma Garima G Sowpati Divya Tej DT Singh Prakruti P Khan Mehak Zahoor MZ Ganji Rakesh R Upadhyay Sandeep S Banerjee Sharmistha S Nandicoori Vinay Kumar VK Khosla Sanjeev S

Scientific reports 20160426

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 ...[more]

PMID: 27112593

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Project description:DNA CpG methylation is a widespread epigenetic mark in high eukaryotes including mammals. DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and control of gene expression. Recent advancements in sequencing-based DNA methylation profiling methods provide an unprecedented opportunity to measure DNA methylation in a genome-wide fashion, making it possible to comprehensively investigate the role of DNA methylation. Several methods have been developed, such as Whole Genome Bisulfite Sequencing (WGBS), Reduced Representation Bisulfite Sequencing (RRBS), and enrichment-based methods including Methylation Dependent ImmunoPrecipitation followed by sequencing (MeDIP-seq), methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), methyltransferase-directed Transfer of Activated Groups followed by sequencing (mTAG), and Methylation-sensitive Restriction Enzyme digestion followed by sequencing (MRE-seq). These methods differ by their genomic CpG coverage, resolution, quantitative accuracy, cost, and software for analyzing the data. Among these, WGBS is considered the gold standard. However, it is still a cost-prohibitive technology for a typical laboratory due to the required sequencing depth. We found that by integrating two enrichment-based methods that are complementary in nature (i.e., MeDIP-seq and MRE-seq), we can significantly increase the efficiency of whole DNA methylome profiling. By using two recently developed computational algorithms (i.e., M&M and methylCRF), the combination of MeDIP-seq and MRE-seq produces genome-wide CpG methylation measurement at high coverage and high resolution, and robust predictions of differentially methylated regions. Thus, the combination of the two enrichment-based methods provides a cost-effective alternative to WGBS. In this article we describe both the experimental protocols for performing MeDIP-seq and MRE-seq, and the computational protocols for running M&M and methylCRF.

Dataset Information

Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection.

Publications

Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection.

Similar Datasets

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