Formation of distinct chromatin conformation signatures epigenetically regulate macrophage activation

Subhankar Mukhopadhyay, Aroul Selvam Ramadass, Alexandre Akoulitchev*, Siamon Gordon

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

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.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalInternational Immunopharmacology
Volume18
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Chromatin conformation
  • Epigenetics
  • Macrophage activation

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