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Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers

Author

Listed:
  • James A. Oo

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

  • Timothy Warwick

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

  • Katalin Pálfi

    (Institute for Cardiovascular Physiology)

  • Frederike Lam

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

  • Francois McNicoll

    (Institute for Molecular Biosciences)

  • Cristian Prieto-Garcia

    (Faculty of Medicine
    Buchmann Institute for Molecular Life Sciences)

  • Stefan Günther

    (Max Planck Institute for Heart and Lung Research)

  • Can Cao

    (Institute for Cardiovascular Physiology
    Heidelberg University Hospital
    Partner site Heidelberg/Mannheim)

  • Yinuo Zhou

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

  • Alexey A. Gavrilov

    (Russian Academy of Sciences)

  • Sergey V. Razin

    (Russian Academy of Sciences
    Lomonosov Moscow State University)

  • Alfredo Cabrera-Orefice

    (Institute for Cardiovascular Physiology
    Functional Proteomics Center)

  • Ilka Wittig

    (Institute for Cardiovascular Physiology
    Functional Proteomics Center)

  • Soni Savai Pullamsetti

    (Justus Liebig University
    University of Giessen)

  • Leo Kurian

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

  • Ralf Gilsbach

    (Institute for Cardiovascular Physiology
    Heidelberg University Hospital
    Partner site Heidelberg/Mannheim)

  • Marcel H. Schulz

    (Partner site Rhein/Main
    Goethe University Frankfurt
    Institute for Computational Genomic Medicine)

  • Ivan Dikic

    (Goethe University Frankfurt
    Faculty of Medicine
    Buchmann Institute for Molecular Life Sciences)

  • Michaela Müller-McNicoll

    (Goethe University Frankfurt
    Institute for Molecular Biosciences
    Max Planck Institute for Biophysics)

  • Ralf P. Brandes

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

  • Matthias S. Leisegang

    (Institute for Cardiovascular Physiology
    Partner site Rhein/Main
    Goethe University Frankfurt)

Abstract

The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state. It does so while retaining the ability to respond dynamically to cellular signals. However, the mechanisms that guide SWI/SNF to specific genomic targets have remained elusive. Here we demonstrate that trans-acting long non-coding RNAs (lncRNAs) direct the SWI/SNF complex to cell type-specific enhancers. SWI/SNF preferentially binds lncRNAs and these predominantly bind DNA targets in trans. Together they localize to enhancers, many of which are cell type-specific. Knockdown of SWI/SNF- and enhancer-bound lncRNAs causes the genome-wide redistribution of SWI/SNF away from enhancers and a concomitant differential expression of spatially connected target genes. These lncRNA-SWI/SNF-enhancer networks support an enhancer hub model of SWI/SNF genomic targeting. Our findings reveal that lncRNAs competitively recruit SWI/SNF, providing a specific and dynamic layer of control over chromatin accessibility, and reinforcing their role in mediating enhancer activity and gene expression.

Suggested Citation

  • James A. Oo & Timothy Warwick & Katalin Pálfi & Frederike Lam & Francois McNicoll & Cristian Prieto-Garcia & Stefan Günther & Can Cao & Yinuo Zhou & Alexey A. Gavrilov & Sergey V. Razin & Alfredo Cabr, 2025. "Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55539-6
    DOI: 10.1038/s41467-024-55539-6
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    References listed on IDEAS

    as
    1. Burak H. Alver & Kimberly H. Kim & Ping Lu & Xiaofeng Wang & Haley E. Manchester & Weishan Wang & Jeffrey R. Haswell & Peter J. Park & Charles W. M. Roberts, 2017. "The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    2. Lanbo Xiao & Abhijit Parolia & Yuanyuan Qiao & Pushpinder Bawa & Sanjana Eyunni & Rahul Mannan & Sandra E. Carson & Yu Chang & Xiaoju Wang & Yuping Zhang & Josh N. Vo & Steven Kregel & Stephanie A. Si, 2022. "Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer," Nature, Nature, vol. 601(7893), pages 434-439, January.
    3. Debashish U. Menon & Oleksandr Kirsanov & Christopher B. Geyer & Terry Magnuson, 2021. "Mammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
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