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MyoD1 localization at the nuclear periphery is mediated by association of WFS1 with active enhancers

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  • Konstantina Georgiou

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna
    a Doctoral School of the University of Vienna and Medical University of Vienna)

  • Fatih Sarigol

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna)

  • Tobias Nimpf

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna)

  • Christian Knapp

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna
    The Barcelona Institute of Science and Technology)

  • Daria Filipczak

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna
    a Doctoral School of the University of Vienna and Medical University of Vienna)

  • Roland Foisner

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna)

  • Nana Naetar

    (Max Perutz Labs, Vienna Biocenter Campus (VBC)
    Max Perutz Labs, Medical University of Vienna)

Abstract

Spatial organization of the mammalian genome influences gene expression and cell identity. While association of genes with the nuclear periphery is commonly linked to transcriptional repression, also active, expressed genes can localize at the nuclear periphery. The transcriptionally active MyoD1 gene, a master regulator of myogenesis, exhibits peripheral localization in proliferating myoblasts, yet the underlying mechanisms remain elusive. Here, we generate a reporter cell line to demonstrate that peripheral association of the MyoD1 locus is independent of mechanisms involved in heterochromatin anchoring. Instead, we identify the nuclear envelope transmembrane protein WFS1 that tethers MyoD1 to the nuclear periphery. WFS1 primarily associates with active distal enhancer elements upstream of MyoD1, and with a subset of enhancers genome-wide, which are enriched in active histone marks and linked to expressed myogenic genes. Overall, our data identify a mechanism involved in tethering regulatory elements of active genes to the nuclear periphery.

Suggested Citation

  • Konstantina Georgiou & Fatih Sarigol & Tobias Nimpf & Christian Knapp & Daria Filipczak & Roland Foisner & Nana Naetar, 2025. "MyoD1 localization at the nuclear periphery is mediated by association of WFS1 with active enhancers," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57758-x
    DOI: 10.1038/s41467-025-57758-x
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    References listed on IDEAS

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    1. Lars Guelen & Ludo Pagie & Emilie Brasset & Wouter Meuleman & Marius B. Faza & Wendy Talhout & Bert H. Eussen & Annelies de Klein & Lodewyk Wessels & Wouter de Laat & Bas van Steensel, 2008. "Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions," Nature, Nature, vol. 453(7197), pages 948-951, June.
    2. K. L. Reddy & J. M. Zullo & E. Bertolino & H. Singh, 2008. "Transcriptional repression mediated by repositioning of genes to the nuclear lamina," Nature, Nature, vol. 452(7184), pages 243-247, March.
    3. Linlin Wang & Hongyang Liu & Xiaofei Zhang & Eli Song & You Wang & Tao Xu & Zonghong Li, 2021. "WFS1 functions in ER export of vesicular cargo proteins in pancreatic β-cells," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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