Epromoters function as a hub to recruit key transcription factors required for the inflammatory response


  • Santiago-Algarra David
  • Souaid Charbel
  • Singh Himanshu
  • Dao Lan T M
  • Hussain Saadat
  • Medina-Rivera Alejandra
  • Ramirez-Navarro Lucia
  • Castro-Mondragon Jaime A
  • Sadouni Nori
  • Charbonnier Guillaume
  • Spicuglia Salvatore


  • Gene regulation
  • Inflammation

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Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.

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