First study of the role of transcribed enhancers in macrophage response to M.tb
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (M.tb). M.tb escapes the host immune response by entering host macrophages and building a favourable niche. Macrophages can control or eliminate the M.tb if they acquire the correct phenotypes, these phenotypes are activated and maintained by transcriptional regulation. Transcriptional enhancers are key in transcriptional regulation, the researchers explored them in their recent paper, the first study of its kind.
Transcribed enhancers in M.tb-infected macrophages were studied which allowed the researchers to establish “a link between known M.tb-responsive transcription factors and transcriptional activation of enhancers and their target genes”. This suggests that enhancers may drive the macrophage response via transcriptional activation of key immune genes. It was also found that enhancers acquire transcription de novo upon infection. Lastly, highly transcriptionally induced enhancers have been linked to activation of genes that have previously been undervalued in M.tb infection.
M.tb triggers many changes in macrophage gene expression but the regulatory mechanisms behind these changes are not well understood. This study of transcribed enhancers in macrophage response to M.tb infection extends understanding of the regulation of M.tb responses “by linking M.tb-responsive transcription factors to activation of transcribed enhancers, which, in turn, target protein-coding immune genes upon infection”. Associate Prof. Guler and Prof. Brombacher et al believe that given the recent advances in enhancer and chromatin-directed therapy, their study may help pave the way for further research towards host-directed therapy and new TB treatments.
Read the paper - Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
Article by Bonamy Holtak