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

Autor: Santiago-Algarra D; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Souaid C; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Singh H; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Dao LTM; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France.; Vinmec Research Institute of Stem cell and Gene technology, Vinmec Healthcare System, Hanoi, Vietnam., Hussain S; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Medina-Rivera A; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla, Mexico., Ramirez-Navarro L; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla, Mexico., Castro-Mondragon JA; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, 0318, Oslo, Norway., Sadouni N; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Charbonnier G; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Spicuglia S; Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France. salvatore.spicuglia@inserm.fr.; Equipe Labellisée Ligue Contre le Cancer, Paris, France. salvatore.spicuglia@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Nov 18; Vol. 12 (1), pp. 6660. Date of Electronic Publication: 2021 Nov 18.
DOI: 10.1038/s41467-021-26861-0
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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