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

David Santiago-Algarra (1) , Charbel Souaid (1) , Himanshu Singh (1) , Lan T M Dao (1) , Saadat Hussain (1) , Alejandra Medina-Rivera (2) , Lucia Ramirez-Navarro (2) , Jaime A Castro-Mondragon (1) , Nori Sadouni (1) , Guillaume Charbonnier (1) , Salvatore Spicuglia (1)

1 TAGC - Theories and Approaches of Genomic Complexity
2 UNAM - Universidad Nacional Autónoma de México = National Autonomous University of Mexico

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.

Mots clés: Gene regulation; Inflammation

Domaines: Sciences du Vivant [q-bio]; Génomique, Transcriptomique et Protéomique [q-bio.GN]

David Santiago-Algarra, Charbel Souaid, Himanshu Singh, Lan T M Dao, Saadat Hussain, et al.. Epromoters function as a hub to recruit key transcription factors required for the inflammatory response. Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-26861-0⟩. ⟨hal-03513051⟩