Genome-wide profiling of transcribed enhancers during macrophage activation

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dc.contributor.authorDenisenko, Elena
dc.contributor.authorGuler, Reto
dc.contributor.authorMhlanga, Musa M
dc.contributor.authorSuzuki, Harukazu
dc.contributor.authorBrombacher, Frank
dc.contributor.authorSchmeier, Sebastian
dc.date.accessioned2017-10-30T12:05:26Z
dc.date.available2017-10-30T12:05:26Z
dc.date.issued2017-10-23
dc.date.updated2017-10-29T12:43:15Z
dc.description.abstractBackground: 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.identifier.apacitationDenisenko, E., Guler, R., Mhlanga, M. M., Suzuki, H., Brombacher, F., & Schmeier, S. (2017). Genome-wide profiling of transcribed enhancers during macrophage activation. <i>Epigenetics & Chromatin</i>, http://hdl.handle.net/11427/25906en_ZA
dc.identifier.chicagocitationDenisenko, Elena, Reto Guler, Musa M Mhlanga, Harukazu Suzuki, Frank Brombacher, and Sebastian Schmeier "Genome-wide profiling of transcribed enhancers during macrophage activation." <i>Epigenetics & Chromatin</i> (2017) http://hdl.handle.net/11427/25906en_ZA
dc.identifier.citationDenisenko, 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.identifier.ris TY - Journal Article AU - Denisenko, Elena AU - Guler, Reto AU - Mhlanga, Musa M AU - Suzuki, Harukazu AU - Brombacher, Frank AU - Schmeier, Sebastian AB - 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. DA - 2017-10-23 DB - OpenUCT DO - 10.1186/s13072-017-0158-9 DP - University of Cape Town J1 - Epigenetics & Chromatin LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Genome-wide profiling of transcribed enhancers during macrophage activation TI - Genome-wide profiling of transcribed enhancers during macrophage activation UR - http://hdl.handle.net/11427/25906 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s13072-017-0158-9
dc.identifier.urihttp://hdl.handle.net/11427/25906
dc.identifier.vancouvercitationDenisenko E, Guler R, Mhlanga MM, Suzuki H, Brombacher F, Schmeier S. Genome-wide profiling of transcribed enhancers during macrophage activation. Epigenetics & Chromatin. 2017; http://hdl.handle.net/11427/25906.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDivision of Infectious Disease and HIV Meden_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s)
dc.sourceEpigenetics & Chromatin
dc.source.urihttps://epigeneticsandchromatin.biomedcentral.com/
dc.subject.otherTranscriptional enhancers
dc.subject.othereRNA
dc.subject.otherTranscriptional regulation
dc.subject.otherMacrophage activation
dc.titleGenome-wide profiling of transcribed enhancers during macrophage activation
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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