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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 sec...

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Main Authors: Cordero, Julio (Author) , Swaminathan, Guruprasadh (Author) , Rogel-Ayala, Diana G. (Author) , Rubio Nava, Karla Maria (Author) , Elsherbiny, Adel (Author) , Mahmood, Samina (Author) , Szymański, Witold (Author) , Graumann, Johannes (Author) , Braun, Thomas (Author) , Günther, Stefan (Author) , Dobreva, Gergana (Author) , Barreto, Guillermo (Author)
Format: Article (Journal)
Language:English
Published: 20 December 2024
In: Nature Communications
Year: 2024, Volume: 15, Pages: 1-21
ISSN:2041-1723
DOI:10.1038/s41467-024-54740-x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-024-54740-x
Verlag, lizenzpflichtig, Volltext: http://www.nature.com/articles/s41467-024-54740-x
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Author Notes:Julio Cordero, Guruprasadh Swaminathan, Diana G. Rogel-Ayala, Karla Rubio, Adel Elsherbiny, Samina Mahmood, Witold Szymanski, Johannes Graumann, Thomas Braun, Stefan Günther, Gergana Dobreva and Guillermo Barreto
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Summary: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.
Item Description:Im Titel ist "TGF-β-induced transcription" mit einem griechischen Buchstaben geschrieben
Gesehen am 07.04.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-54740-x

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