ArticlePLoS pathogens2013
DNA methylation impacts gene expression and ensures hypoxic survival of Mycobacterium tuberculosis.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 172 citations in OpenAlex.
- Article
- Epigenetic regulation in prokaryotes: transcriptional and phenotypic outcomes of DNA methyltransferase activity.FEMS microbiology reviews · 2026Review
- Genome-wide transcriptional landscape ofFrontiers in immunology · 2026Article
- The pathway of autophagy in the epigenetic landscape ofAutophagy · 2025Review
- Article
- Dam-dependent epigenetic memory regulates prophage reintegration in Salmonella.Nucleic acids research · 2025Article
- The emerging role of DNA methylation in the pathogenicity of bacterial pathogens.Journal of bacteriology · 2025Review
- Genomic Insight into Primary Adaptation ofAntibiotics (Basel, Switzerland) · 2025Article
- Understanding prokaryotic adaptation through advanced DNA methylation detection techniques.The ISME journal · 2025Review
- Epigenetic Mechanisms Induced byInternational journal of molecular sciences · 2024Review
- Intercellular mosaic methylation in fast-growingNAR molecular medicine · 2024Article
- Extensive differential DNA methylation between tuberculosis skin test positive and skin test negative cattle.BMC genomics · 2024Article
- Transcriptome analysis and molecular characterization of novel small RNAs in Mycobacterium tuberculosis Lineage 1.World journal of microbiology & biotechnology · 2024Article
- The Restriction Activity Investigation of Rv2528c, an Mrr-like Modification-Dependent Restriction Endonuclease fromMicroorganisms · 2024Article
- Moving toward the Inclusion of Epigenomics in Bacterial Genome Evolution: Perspectives and Challenges.International journal of molecular sciences · 2024Review
- A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways inbioRxiv : the preprint server for biology · 2024Article
- Important role of DNA methylation hints at significant potential in tuberculosis.Archives of microbiology · 2024Review
- Exploring the memory of the gut microbiome: a multifaceted perspective.Frontiers in microbiomes · 2024Article
- Article
- The future of cancer immunotherapy: DNA vaccines leading the way.Medical oncology (Northwood, London, England) · 2023Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
DNA methylation regulates gene expression in many organisms. In eukaryotes, DNA methylation is associated with gene repression, while it exerts both activating and repressive effects in the Proteobacteria through largely locus-specific mechanisms. Here, we identify a critical DNA methyltransferase in M. tuberculosis, which we term MamA. MamA creates N⁶-methyladenine in a six base pair recognition sequence present in approximately 2,000 copies on each strand of the genome. Loss of MamA reduces the expression of a number of genes. Each has a MamA site located at a conserved position relative to the sigma factor -10 binding site and transcriptional start site, suggesting that MamA modulates their expression through a shared, not locus-specific, mechanism. While strains lacking MamA grow normally in vitro, they are attenuated in hypoxic conditions, suggesting that methylation promotes survival in discrete host microenvironments. Interestingly, we demonstrate strikingly different patterns of DNA methyltransferase activity in different lineages of M. tuberculosis, which have been associated with preferences for distinct host environments and different disease courses in humans. Thus, MamA is the major functional adenine methyltransferase in M. tuberculosis strains of the Euro-American lineage while strains of the Beijing lineage harbor a point mutation that largely inactivates MamA but possess a second functional DNA methyltransferase. Our results indicate that MamA influences gene expression in M. tuberculosis and plays an important but strain-specific role in fitness during hypoxia.
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