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

Author

Listed:
  • Julio Cordero

    (Heidelberg University
    German Centre for Cardiovascular Research (DZHK)
    Max-Planck-Institute for Heart and Lung Research)

  • Guruprasadh Swaminathan

    (UMR 7365)

  • Diana G. Rogel-Ayala

    (Max-Planck-Institute for Heart and Lung Research
    UMR 7365)

  • Karla Rubio

    (Max-Planck-Institute for Heart and Lung Research
    UMR 7365
    Massachusetts General Hospital and Harvard Medical School
    Benemérita Universidad Autónoma de Puebla)

  • Adel Elsherbiny

    (Heidelberg University
    German Centre for Cardiovascular Research (DZHK))

  • Samina Mahmood

    (Max-Planck-Institute for Heart and Lung Research)

  • Witold Szymanski

    (Philipps-University Marburg)

  • Johannes Graumann

    (Philipps-University Marburg)

  • Thomas Braun

    (Max-Planck-Institute for Heart and Lung Research)

  • Stefan Günther

    (Max-Planck-Institute for Heart and Lung Research
    Max-Planck-Institute for Heart and Lung Research)

  • Gergana Dobreva

    (Heidelberg University
    German Centre for Cardiovascular Research (DZHK)
    Helmholtz-Institute for Translational AngioCardioScience (HI-TAC) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) at Heidelberg University)

  • Guillermo Barreto

    (Max-Planck-Institute for Heart and Lung Research
    UMR 7365)

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.

Suggested Citation

  • Julio Cordero & Guruprasadh Swaminathan & Diana G. Rogel-Ayala & Karla Rubio & Adel Elsherbiny & Samina Mahmood & Witold Szymanski & Johannes Graumann & Thomas Braun & Stefan Günther & Gergana Dobreva, 2024. "Nuclear microRNA 9 mediates G-quadruplex formation and 3D genome organization during TGF-β-induced transcription," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54740-x
    DOI: 10.1038/s41467-024-54740-x
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