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

Konstantina Georgiou, Fatih Sarigol, Tobias Nimpf, Christian Knapp, Daria Filipczak, Roland Foisner () and Nana Naetar ()
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Konstantina Georgiou: Max Perutz Labs, Vienna Biocenter Campus (VBC)
Fatih Sarigol: Max Perutz Labs, Vienna Biocenter Campus (VBC)
Tobias Nimpf: Max Perutz Labs, Vienna Biocenter Campus (VBC)
Christian Knapp: Max Perutz Labs, Vienna Biocenter Campus (VBC)
Daria Filipczak: Max Perutz Labs, Vienna Biocenter Campus (VBC)
Roland Foisner: Max Perutz Labs, Vienna Biocenter Campus (VBC)
Nana Naetar: Max Perutz Labs, Vienna Biocenter Campus (VBC)

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-57758-x

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