Journal
EPIGENETICS & CHROMATIN
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13072-017-0158-9
Keywords
Transcriptional enhancers; eRNA; Transcriptional regulation; Macrophage activation
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Funding
- South African National Research Foundation (NRF)
- Department of Science and Technology, South African Research Chair Initiative (SARCHi)
- South Africa Medical Research Council (SAMRC)
- National Research Foundation of South Africa
- South African National Research Foundation (NRF) Competitive Programme for Unrated Researchers (CSUR)
- Japan Society for the Promotion of Science (JSPS)
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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-.(gamma) 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-gamma) 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.
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