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Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
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Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
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Journal Article
Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
2019
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
