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An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome.

Gomez-Gonzalez, PJ; Andreu, N; Phelan, JE; de Sessions, PF; Glynn, JR; Crampin, AC; Campino, S; Butcher, PD; Hibberd, ML; Clark, TG (2019) An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome. Sci Rep, 9 (1). p. 5204. ISSN 2045-2322 https://doi.org/10.1038/s41598-019-41692-2
SGUL Authors: Butcher, Philip David

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Abstract

Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. However, so far no studies have integrated sequence-based genomic, transcriptomic and methylation characterisation across a common set of samples, which is critical to understand how DNA sequence and methylation affect RNA expression and, ultimately, Mtb pathogenesis. Here we perform such an integrated analysis across 22 M. tuberculosis clinical isolates, representing ancient (lineage 1) and modern (lineages 2 and 4) strains. The results confirm the presence of lineage-specific differential gene expression, linked to specific SNP-based expression quantitative trait loci: with 10 eQTLs involving SNPs in promoter regions or transcriptional start sites; and 12 involving potential functional impairment of transcriptional regulators. Methylation status was also found to have a role in transcription, with evidence of differential expression in 50 genes across lineage 4 samples. Lack of methylation was associated with three novel variants in mamA, likely to cause loss of function of this enzyme. Overall, our work shows the relationship of DNA sequence and methylation to RNA expression, and differences between ancient and modern lineages. Further studies are needed to verify the functional consequences of the identified mechanisms of gene expression regulation.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2019
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Sci Rep
ISSN: 2045-2322
Language: eng
Dates:
DateEvent
26 March 2019Published
14 March 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MR/M01360X/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/R025576/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/R020973/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/N010469/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/R013063/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
261868591British Councilhttp://dx.doi.org/10.13039/501100000308
PubMed ID: 30914757
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110782
Publisher's version: https://doi.org/10.1038/s41598-019-41692-2

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