The Nuclear Envelope Protein Net39 is Essential for Muscle Nuclear Integrity and Chromatin Organization

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 30

PMID 33514739

Citations 15

Authors

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

Affiliations

Soon will be listed here.

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.

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