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Epigenetics Chromatin. 2017 Oct 23;10(1):50. doi: 10.1186/s13072-017-0158-9.

Genome-wide profiling of transcribed enhancers during macrophage activation.

Author information

1
Institute of Natural and Mathematical Sciences, Massey University, Albany, Auckland, 0632, New Zealand.
2
Division of Immunology, Institute of Infectious Diseases and Molecular Medicine (IDM), South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
3
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, 7925, South Africa.
4
Gene Expression and Biophysics Group, CSIR Synthetic Biology ERA, Pretoria, 0001, South Africa.
5
Division of Chemical Systems and Synthetic Biology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, 7925, South Africa.
6
Gene Expression and Biophysics Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisbon, Portugal.
7
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
8
Institute of Natural and Mathematical Sciences, Massey University, Albany, Auckland, 0632, New Zealand. s.schmeier@massey.ac.nz.

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.

KEYWORDS:

Macrophage activation; Transcriptional enhancers; Transcriptional regulation; eRNA

PMID:
29061167
PMCID:
PMC5654053
DOI:
10.1186/s13072-017-0158-9
[Indexed for MEDLINE]
Free PMC Article

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