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

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dc.contributor.authorDenisenko, Elena
dc.contributor.authorGuler, Reto
dc.contributor.authorMhlanga, Musa
dc.contributor.authorSuzuki, Harukazu
dc.contributor.authorBrombacher, Frank
dc.contributor.authorSchmeier, Sebastian
dc.date.accessioned2019-02-06T09:08:51Z
dc.date.available2019-02-06T09:08:51Z
dc.date.issued2019-01-22
dc.date.updated2019-01-27T04:20:22Z
dc.description.abstractBackground 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.identifier.apacitationDenisenko, E., Guler, R., Mhlanga, M., Suzuki, H., Brombacher, F., & Schmeier, S. (2019). Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection. http://hdl.handle.net/11427/29343en_ZA
dc.identifier.chicagocitationDenisenko, Elena, Reto Guler, Musa Mhlanga, Harukazu Suzuki, Frank Brombacher, and Sebastian Schmeier "Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection." (2019) http://hdl.handle.net/11427/29343en_ZA
dc.identifier.citationDenisenko, 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.ris TY - Journal Article AU - Denisenko, Elena AU - Guler, Reto AU - Mhlanga, Musa AU - Suzuki, Harukazu AU - Brombacher, Frank AU - Schmeier, Sebastian AB - 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. DA - 2019-01-22 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PY - 2019 T1 - Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection TI - Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection UR - http://hdl.handle.net/11427/29343 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12864-019-5450-6
dc.identifier.urihttp://hdl.handle.net/11427/29343
dc.identifier.vancouvercitationDenisenko E, Guler R, Mhlanga M, Suzuki H, Brombacher F, Schmeier S. Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection. 2019; http://hdl.handle.net/11427/29343.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.rights.holderThe Author(s).
dc.subject.othereRNA
dc.subject.otherMacrophages
dc.subject.otherTranscriptional enhancers
dc.subject.otherTranscriptional regulation
dc.subject.otherTuberculosis
dc.titleTranscriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
dc.typeJournal Article
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