Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription
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.
Authors
- Thomas Braun (ORCID: https://orcid.org/0000-0002-6165-4804)
- Diana G. Rogel-Ayala (ORCID: https://orcid.org/0009-0004-3343-286X)
- Gergana D. Dobreva (ORCID: https://orcid.org/0000-0002-4814-9416)
- Guillermo Barreto (ORCID: https://orcid.org/0000-0002-7777-4712)
- Guruprasadh Swaminathan (ORCID: https://orcid.org/0009-0005-4727-2032)
- Julio Cordero (ORCID: https://orcid.org/0000-0002-2136-1783)
- Stefan Günther (ORCID: https://orcid.org/0000-0002-5594-4549)
- Johannes Graumann (ORCID: https://orcid.org/0000-0002-3015-5850)
- Karla Rubio (ORCID: https://orcid.org/0000-0002-8337-3106)
- Samina Mahmood
- Witold Szymański (ORCID: https://orcid.org/0000-0002-1202-3299)
- Adel Elsherbiny (ORCID: https://orcid.org/0000-0001-8674-2969)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Max Delbrück Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Massachusetts General Hospital (US)
- Max Planck Institute for Heart and Lung Research (DE)
- German Centre for Cardiovascular Research (DE)
- Ingénierie Moléculaire et Physiopathologie Articulaire (FR)
- Benemérita Universidad Autónoma de Puebla (MX)
- Heidelberg University (US)
- Epigenomics (Germany) (DE)
- Université de Lorraine (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1038/s41467-024-54740-x
- Citations
- 11
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- Baden-Württemberg Stiftung
- Deutsches Zentrum für Herz-Kreislaufforschung
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Universität Heidelberg
- Bundesministerium für Bildung und Forschung
- Max-Planck-Gesellschaft
- Centre National de la Recherche Scientifique
- Cardio-Pulmonary Institute