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The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

Author

Listed:
  • Andres Ramirez-Martinez

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Yichi Zhang

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Kenian Chen

    (Quantitative Biomedical Research Center University of Texas Southwestern Medical Center)

  • Jiwoong Kim

    (Quantitative Biomedical Research Center University of Texas Southwestern Medical Center)

  • Bercin K. Cenik

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Northwestern University Feinberg School of Medicine)

  • John R. McAnally

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Chunyu Cai

    (University of Texas Southwestern Medical Center)

  • John M. Shelton

    (University of Texas Southwestern Medical Center)

  • Jian Huang

    (University of Texas Southwestern Medical Center)

  • Ana Brennan

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Bret M. Evers

    (University of Texas Southwestern Medical Center)

  • Pradeep P. A. Mammen

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Lin Xu

    (Quantitative Biomedical Research Center University of Texas Southwestern Medical Center)

  • Rhonda Bassel-Duby

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Ning Liu

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Eric N. Olson

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

Abstract

Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism. These abnormalities resemble those of Emery–Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.

Suggested Citation

  • Andres Ramirez-Martinez & Yichi Zhang & Kenian Chen & Jiwoong Kim & Bercin K. Cenik & John R. McAnally & Chunyu Cai & John M. Shelton & Jian Huang & Ana Brennan & Bret M. Evers & Pradeep P. A. Mammen , 2021. "The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20987-x
    DOI: 10.1038/s41467-021-20987-x
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    Cited by:

    1. Matthieu Dos Santos & Akansha M. Shah & Yichi Zhang & Svetlana Bezprozvannaya & Kenian Chen & Lin Xu & Weichun Lin & John R. McAnally & Rhonda Bassel-Duby & Ning Liu & Eric N. Olson, 2023. "Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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