Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection

 

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dc.contributor.author Denisenko, Elena
dc.contributor.author Guler, Reto
dc.contributor.author Mhlanga, Musa
dc.contributor.author Suzuki, Harukazu
dc.contributor.author Brombacher, Frank
dc.contributor.author Schmeier, Sebastian
dc.date.accessioned 2019-02-06T09:08:51Z
dc.date.available 2019-02-06T09:08:51Z
dc.date.issued 2019-01-22
dc.identifier.citation Denisenko, E., Guler, R., Mhlanga, M., Suzuki, H., Brombacher, F., & Schmeier, S. (2019). Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection. BMC genomics, 20(1), 71.
dc.identifier.uri https://doi.org/10.1186/s12864-019-5450-6
dc.identifier.uri http://hdl.handle.net/11427/29343
dc.description.abstract Background Tuberculosis is a life-threatening infectious disease caused by Mycobacterium tuberculosis (M.tb). M.tb subverts host immune responses to build a favourable niche and survive inside of host macrophages. Macrophages can control or eliminate the infection, if acquire appropriate functional phenotypes. Transcriptional regulation is a key process that governs the activation and maintenance of these phenotypes. Among the factors orchestrating transcriptional regulation during M.tb infection, transcriptional enhancers still remain unexplored. Results We analysed transcribed enhancers in M.tb-infected mouse bone marrow-derived macrophages. We established a link between known M.tb-responsive transcription factors and transcriptional activation of enhancers and their target genes. Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. We report enhancers acquiring transcription de novo upon infection. Finally, we link highly transcriptionally induced enhancers to activation of genes with previously unappreciated roles in M.tb infection, such as Fbxl3, Tapt1, Edn1, and Hivep1. Conclusions Our findings suggest the importance of macrophage host transcriptional enhancers during M.tb infection. Our study extends current knowledge of the regulation of macrophage responses to M.tb infection and provides a basis for future functional studies on enhancer-gene interactions in this process.
dc.language.iso en
dc.publisher BioMed Central
dc.subject.other eRNA
dc.subject.other Macrophages
dc.subject.other Transcriptional enhancers
dc.subject.other Transcriptional regulation
dc.subject.other Tuberculosis
dc.title Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
dc.type Journal Article
dc.date.updated 2019-01-27T04:20:22Z
dc.rights.holder The Author(s).


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