Fiche publication
Date publication
décembre 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARRETO Guillermo
Tous les auteurs :
Cordero J, Swaminathan G, Rogel-Ayala DG, Rubio K, Elsherbiny A, Mahmood S, Szymanski W, Graumann J, Braun T, Günther S, Dobreva G, Barreto G
Lien Pubmed
Résumé
The dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression. However, the role of G4s in promoter-distal regulatory elements, such as super-enhancers (SE), and in chromatin looping has remained elusive. Here we show that mature microRNA 9 (miR-9) is enriched at promoters and SE of genes that are inducible by transforming growth factor beta 1 (TGFB1) signaling. Moreover, we find that miR-9 is required for formation of G4s, promoter-super-enhancer looping and broad domains of the euchromatin histone mark H3K4me3 at TGFB1-responsive genes. Our study places miR-9 in the same functional context with G4s and promoter-enhancer interactions during 3D genome organization and transcriptional activation induced by TGFB1 signaling, a critical signaling pathway in cancer and fibrosis.
Mots clés
MicroRNAs, genetics, G-Quadruplexes, Humans, Promoter Regions, Genetic, Transforming Growth Factor beta1, metabolism, Transcription, Genetic, drug effects, Signal Transduction, Enhancer Elements, Genetic, Chromatin, metabolism, Gene Expression Regulation, Animals, Cell Nucleus, metabolism, Histones, metabolism, Transcriptional Activation, Genome, Human
Référence
Nat Commun. 2024 12 20;15(1):10711