Genome-wide profiling of transcribed enhancers during macrophage activation


Show simple item record Denisenko, Elena Guler, Reto Mhlanga, Musa M Suzuki, Harukazu Brombacher, Frank Schmeier, Sebastian 2017-10-30T12:05:26Z 2017-10-30T12:05:26Z 2017-10-23
dc.identifier.citation Denisenko, E., Guler, R., Mhlanga, M. M., Suzuki, H., Brombacher, F., & Schmeier, S. (2017). Genome-wide profiling of transcribed enhancers during macrophage activation. Epigenetics & Chromatin, 10(1), 50.
dc.description.abstract Background: Macrophages are sentinel cells essential for tissue homeostasis and host defence. Owing to their plasticity, macrophages acquire a range of functional phenotypes in response to microenvironmental stimuli, of which M(IFN-γ) and M(IL-4/IL-13) are well known for their opposing pro- and anti-inflammatory roles. Enhancers have emerged as regulatory DNA elements crucial for transcriptional activation of gene expression. Results: Using cap analysis of gene expression and epigenetic data, we identify on large-scale transcribed enhancers in bone marrow-derived mouse macrophages, their time kinetics, and target protein-coding genes. We observe an increase in target gene expression, concomitant with increasing numbers of associated enhancers, and find that genes associated with many enhancers show a shift towards stronger enrichment for macrophage-specific biological processes. We infer enhancers that drive transcriptional responses of genes upon M(IFN-γ) and M(IL-4/IL-13) macrophage activation and demonstrate stimuli specificity of regulatory associations. Finally, we show that enhancer regions are enriched for binding sites of inflammation-related transcription factors, suggesting a link between stimuli response and enhancer transcriptional control. Conclusions: Our study provides new insights into genome-wide enhancer-mediated transcriptional control of macrophage genes, including those implicated in macrophage activation, and offers a detailed genome-wide catalogue of transcribed enhancers in bone marrow-derived mouse macrophages.
dc.language.iso en
dc.publisher BioMed Central
dc.source Epigenetics & Chromatin
dc.subject.other Transcriptional enhancers
dc.subject.other eRNA
dc.subject.other Transcriptional regulation
dc.subject.other Macrophage activation
dc.title Genome-wide profiling of transcribed enhancers during macrophage activation
dc.type Journal Article 2017-10-29T12:43:15Z
dc.rights.holder The Author(s)
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Infectious Disease and HIV Med en_ZA
uct.type.filetype Text
uct.type.filetype Image

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