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dc.contributor.authorDoherty, Rachael
dc.contributor.authorWhiston, Ronan
dc.contributor.authorCormican, Paul
dc.contributor.authorFinlay, Emma K.
dc.contributor.authorCouldrey, Christine
dc.contributor.authorBrady, Colm
dc.contributor.authorO’Farrelly, Cliona
dc.contributor.authorMeade, Kieran G
dc.date.accessioned2020-02-13T15:49:35Z
dc.date.available2020-02-13T15:49:35Z
dc.date.issued2016-08-10
dc.identifier.citationDoherty, R., Whiston, R., Cormican, P. et al. The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle. Sci Rep 6, 31014 (2016). https://doi.org/10.1038/srep31014en_US
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11019/1861
dc.descriptionpeer-revieweden_US
dc.description.abstractWe hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle.en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofseriesScientific Reports;Vol. 6
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectCD4+ T cellen_US
dc.subjectMycobacterium bovisen_US
dc.subjectCattleen_US
dc.subjectMicroRNAen_US
dc.subjectInflammationen_US
dc.titleThe CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattleen_US
dc.typeArticleen_US
dc.identifier.doihttps://dx.doi.org/10.1038/srep31014
dc.contributor.sponsorTeagasc Walsh Fellowship Programmeen_US
dc.source.volume6
dc.source.issue1
refterms.dateFOA2020-02-13T15:49:35Z


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