RT Journal Article SR Electronic T1 Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 303552 DO 10.1101/303552 A1 Elena Denisenko A1 Reto Guler A1 Musa Mhlanga A1 Harukazu Suzuki A1 Frank Brombacher A1 Sebastian Schmeier YR 2018 UL http://biorxiv.org/content/early/2018/11/12/303552.abstract 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 appropriate transcriptional programs are activated. The role of transcriptional enhancers in the activation and maintenance of these programs remains 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 the 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 the activation of genes with previously unappreciated roles in M.tb infection, such as Fbxl3, Tapt1, Edn1, and Hivep1.Conclusions Our findings extend current knowledge of the regulation of macrophage responses to M.tb infection and provide a basis for future functional studies on enhancer-gene interactions in this process.