TY - JOUR
T1 - The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization
AU - Ramirez-Martinez, Andres
AU - Zhang, Yichi
AU - Chen, Kenian
AU - Kim, Jiwoong
AU - Cenik, Bercin K.
AU - McAnally, John R.
AU - Cai, Chunyu
AU - Shelton, John M.
AU - Huang, Jian
AU - Brennan, Ana
AU - Evers, Bret M.
AU - Mammen, Pradeep P.A.
AU - Xu, Lin
AU - Bassel-Duby, Rhonda
AU - Liu, Ning
AU - Olson, Eric N.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-20987-x
DO - 10.1038/s41467-021-20987-x
M3 - Article
C2 - 33514739
AN - SCOPUS:85099971183
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 690
ER -