Epromoters function as a hub to recruit key transcription factors required for the inflammatory response
Year: 2021
Type: article
Abstract: 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.
Source: Nature Communications
Authors: David Santiago-Algarra, Charbel Souaid, Himanshu Singh, Lan T. M. Dao, Saadat Hussain, Alejandra Medina-Rivera, Lucia Ramirez-Navarro, Jaime A. Castro-Mondragon, Nori Sadouni, Guillaume Charbonnier, Salvatore Spicuglia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,885
Funders: Aix-Marseille Université, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Consejo Nacional de Ciencia y Tecnología, Ligue Contre le Cancer, Universidad Nacional Autónoma de México, Canceropôle PACA, Institut National Du Cancer, Fondation Bettencourt Schueller, Asociación Nacional de Universidades e Instituciones de Educación Superior
Awards: INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE, G1742243815, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique, Molecular basis of human enhanceropathies, Dissection of coordinated stress responses by novel promoter elements with enhancer activity, G434337789, G4656594441, G4866930200, G5029280039, G541215150, G572841159, Identification & analysis of genomic silencer elements, G6803667113, G7240651115, G7633708271, G782245399, G8333144378, G8485337361
OpenAlex ID: W3213027475