Formation of distinct chromatin conformation signatures epigenetically regulate macrophage activation

Int Immunopharmacol. 2014 Jan;18(1):7-11. doi: 10.1016/j.intimp.2013.10.024. Epub 2013 Nov 6.

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.

Keywords: Chromatin conformation; Epigenetics; Macrophage activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Chromatin / immunology
  • Chromatin / metabolism*
  • Computational Biology
  • Epigenesis, Genetic / immunology
  • Gene Expression Regulation
  • Interferon gamma Receptor
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Lipopolysaccharides / immunology
  • Macrophage Activation* / genetics
  • Macrophages, Peritoneal / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Conformation*
  • Myeloid Differentiation Factor 88 / genetics
  • Orexin Receptors
  • Receptors, Cell Surface / metabolism*
  • Receptors, Interferon / genetics
  • Receptors, Interleukin-4 / genetics
  • Signal Transduction / genetics
  • Transcriptome

Substances

  • Antigens, Surface
  • CD200R1 protein, human
  • Chromatin
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Orexin Receptors
  • Receptors, Cell Surface
  • Receptors, Interferon
  • Receptors, Interleukin-4
  • Interleukin-4
  • Interferon-gamma