title: Formation of distinct chromatin conformation signatures epigenetically regulate macrophage activation.
abstract: Microbial-lipopolysacharide (LPS), interleukin 4 (IL-4) and interferon gamma (IFN-γ) polarise macrophages into "innate", "alternative" and "classical", activation states by selective gene regulation. Expression of MARCO, CD200, CD200R1 (innate), MRC1 (alternative) and H2-Eb1 (classical) selectively marks these distinct activation states. Epigenetic events drive such activation upon stimuli and here we study one such mechanism, chromatin conformation signatures implicated in long-range chromatin interactions that regulate transcriptional switch and gene expression. The EpiSwitch™ technology was used to identify and analyse potential markers bordering such conformational signatures for these genes and juxtaposition of markers was compared between resting and activated macrophages. LPS, IL-4 and IFN-γ selectively altered chromatin conformations of their responsive genes in wild type, but not in MyD88(-/-), IL-4R(-/-) and IFN-γR(-/-) macrophages. In addition, two distinct conformations were observed in CD200R1 after LPS and IFN-γ stimulation. In summary, signal-specific alterations in chromatin conformation provide biomarkers that identify and determine distinct gene expression programmes during macrophage activation.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Oxford BioDynamics, 26 Beaumont Street, Oxford, OX1 2NP, UK.
authors.forename: Aroul Selvam
authors.initials: AS
authors.lastname: Ramadass
authors.affiliation: Oxford BioDynamics, 26 Beaumont Street, Oxford, OX1 2NP, UK. Electronic address: alexandre.akoulitchev@oxfordbiodynamics.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Akoulitchev
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. Electronic address: siamon.gordon@path.ox.ac.uk.
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000276:immunology / Q000378:metabolism*; D019295:Computational Biology; D044127:Epigenesis, Genetic / Q000276:immunology; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008968:Molecular Conformation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D064446:Orexin Receptors; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017471:Receptors, Interferon / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome; D000096743:Interferon gamma Receptor
chemical_list: D000954:Antigens, Surface; D002843:Chromatin; D007371:Interferon-gamma; D015847:Interleukin-4; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D019948:Receptors, Interleukin-4; D000096743:Interferon gamma Receptor; C477337:CD200R1 protein, human; C507780:Myd88 protein, mouse
keywords: Chromatin conformation; Epigenetics; Macrophage activation