Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription.

Autor: Cordero J; Department of Cardiovascular Genomics and Epigenomics, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany. Julio.Cordero@medma.uni-heidelberg.de.; German Centre for Cardiovascular Research (DZHK), 68167, Mannheim, Germany. Julio.Cordero@medma.uni-heidelberg.de.; Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany. Julio.Cordero@medma.uni-heidelberg.de., Swaminathan G; Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000, Nancy, France., Rogel-Ayala DG; Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.; Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000, Nancy, France., Rubio K; Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.; Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000, Nancy, France.; Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.; International Laboratory EPIGEN, Consejo de Ciencia y Tecnología del Estado de Puebla (CONCYTEP), Instituto de Ciencias, EcoCampus, Benemérita Universidad Autónoma de Puebla, 72570, Puebla, Mexico., Elsherbiny A; Department of Cardiovascular Genomics and Epigenomics, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.; German Centre for Cardiovascular Research (DZHK), 68167, Mannheim, Germany., Mahmood S; ECCPS Bioinformatics and Deep Sequencing Platform, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany., Szymanski W; Department of Medicine, Institute of Translational Proteomics & Core Facility Translational Proteomics, Philipps-University Marburg, 35043, Marburg, Germany., Graumann J; Department of Medicine, Institute of Translational Proteomics & Core Facility Translational Proteomics, Philipps-University Marburg, 35043, Marburg, Germany., Braun T; Department of Cardiac Development, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany., Günther S; ECCPS Bioinformatics and Deep Sequencing Platform, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.; Department of Cardiac Development, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany., Dobreva G; Department of Cardiovascular Genomics and Epigenomics, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.; German Centre for Cardiovascular Research (DZHK), 68167, Mannheim, Germany.; Helmholtz-Institute for Translational AngioCardioScience (HI-TAC) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) at Heidelberg University, 69117, Heidelberg, Germany., Barreto G; Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany. Guillermo.Barreto@univ-lorraine.fr.; Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, F-54000, Nancy, France. Guillermo.Barreto@univ-lorraine.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Dec 20; Vol. 15 (1), pp. 10711. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1038/s41467-024-54740-x
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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