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

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Item Type:Article
Title:Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription
Creators: Cordero, J., Swaminathan, G. ORCID logoORCID: https://orcid.org/0009-0005-4727-2032, Rogel-Ayala, D.G. ORCID logoORCID: https://orcid.org/0009-0004-3343-286X, Rubio, K., Elsherbiny, A., Mahmood, S., Szymanski, W. ORCID logoORCID: https://orcid.org/0000-0002-1202-3299, Graumann, J. ORCID logoORCID: https://orcid.org/0000-0002-3015-5850, Braun, T. ORCID logoORCID: https://orcid.org/0000-0002-6165-4804, Günther, S. ORCID logoORCID: https://orcid.org/0000-0002-5594-4549, Dobreva, G. ORCID logoORCID: https://orcid.org/0000-0002-4814-9416 and Barreto, G. ORCID logoORCID: https://orcid.org/0000-0002-7777-4712
Abstract: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.
Keywords:Cell Nucleus, Chromatin, G-Quadruplexes, Gene Expression Regulation, Genetic Enhancer Elements, Genetic Promoter Regions, Genetic Transcription, Histones, Human Genome, MicroRNAs, Signal Transduction, Transcriptional Activation, Transforming Growth Factor beta1, Animals
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:15
Number:1
Page Range:10711
Date:20 December 2024
Official Publication:https://doi.org/10.1038/s41467-024-54740-x
PubMed:View item in PubMed

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