Methylation in Mycobacterium tuberculosis is lineage specific with associated mutations present globally.


Phelan, J; de Sessions, PF; Tientcheu, L; Perdigao, J; Machado, D; Hasan, R; Hasan, Z; Bergval, IL; Anthony, R; McNerney, R; Antonio, M; Portugal, I; Viveiros, M; Campino, S; Hibberd, ML; Clark, TG; (2018) Methylation in Mycobacterium tuberculosis is lineage specific with associated mutations present globally. Scientific reports, 8 (1). p. 160. ISSN 2045-2322 DOI: https://doi.org/10.1038/s41598-017-18188-y

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Abstract

DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M. tuberculosis and 2 lineages of M. africanum, the leading causes of tuberculosis disease in humans. We reveal lineage-specific methylated motifs and strain-specific mutations that are abundant globally and likely to explain loss of function in the respective methyltransferases. Our work provides a set of sixteen new complete reference genomes for the Mycobacterium tuberculosis complex, including complete lineage 5 genomes. Insights into lineage-specific methylomes will further elucidate underlying biological mechanisms and other important phenotypes of the epi-genome.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: TB Centre
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PubMed ID: 29317751
Web of Science ID: 419659600041
URI: http://researchonline.lshtm.ac.uk/id/eprint/4646115

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