Formation of distinct chromatin conformation signatures epigerietically regulate macrophage activation

Microbial-lipopolysacharide (LPS), interleukin 4 (IL-4) and interferon gamma (IFN-gamma) 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 (TM) 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-gamma selectively altered chromatin conformations of their responsive genes in wild type, but not in MyD88(-/-), IL-4R(-/-) and IFN-gamma R-/- macrophages. In addition, two distinct conformations were observed in CD200R1 after LPS and IFIN-gamma stimulation. In summary, signal-specific alterations in chromatin conformation provide biomarkers that identify and determine distinct gene expression programmes during macrophage activation. (C) 2013 Elsevier B.V. All rights reserved.