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

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, Lin Xu, Rhonda Bassel-Duby, Ning Liu, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Article number690
JournalNature communications
Issue number1
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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