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dc.contributor.authorShell, Scarlet S.en_US
dc.contributor.authorPrestwich, Erin G.en_US
dc.contributor.authorBaek, Seung-Hunen_US
dc.contributor.authorShah, Rupal R.en_US
dc.contributor.authorSassetti, Christopher M.en_US
dc.contributor.authorDedon, Peter C.en_US
dc.contributor.authorFortune, Sarah M.en_US
dc.date.accessioned2014-02-18T18:10:53Z
dc.date.issued2013en_US
dc.identifier.citationShell, Scarlet S., Erin G. Prestwich, Seung-Hun Baek, Rupal R. Shah, Christopher M. Sassetti, Peter C. Dedon, and Sarah M. Fortune. 2013. “DNA Methylation Impacts Gene Expression and Ensures Hypoxic Survival of Mycobacterium tuberculosis.” PLoS Pathogens 9 (7): e1003419. doi:10.1371/journal.ppat.1003419. http://dx.doi.org/10.1371/journal.ppat.1003419.en
dc.identifier.issn1553-7366en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11717529
dc.description.abstractDNA 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.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.ppat.1003419en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701705/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectGeneticsen
dc.subjectEpigeneticsen
dc.subjectDNA modificationen
dc.subjectGene Expressionen
dc.subjectDNA transcriptionen
dc.subjectMolecular Geneticsen
dc.subjectGene Regulationen
dc.subjectGene Functionen
dc.subjectMicrobiologyen
dc.subjectBacterial Pathogensen
dc.subjectGram Positiveen
dc.subjectMicrobial Pathogensen
dc.subjectMedicineen
dc.subjectInfectious Diseasesen
dc.subjectBacterial Diseasesen
dc.subjectTuberculosisen
dc.titleDNA Methylation Impacts Gene Expression and Ensures Hypoxic Survival of Mycobacterium tuberculosisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Pathogensen
dash.depositing.authorShell, Scarlet S.en_US
dc.date.available2014-02-18T18:10:53Z
dc.identifier.doi10.1371/journal.ppat.1003419*
dash.contributor.affiliatedShell, Scarlet S.
dash.contributor.affiliatedFortune, Sarah


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