Year: 2026
Type: article
Abstract: Human skeletal muscle comprises myofibers formed by fusion of thousands of myoblasts. This process depends on tightly regulated, muscle-specific fusogens, but its genetic control remains poorly understood. Here, we identify CHAMP1 (Chromosome Alignment Maintaining Phosphoprotein 1) as essential for human myoblast fusion in vitro and in vivo. Genomic and protein-interaction assays reveal a noncanonical role for CHAMP1 as a MyoD cofactor that directly activates expression of the key muscle fusogen Myomaker. As established in prior clinical reports, CHAMP1 mutations in patients cause developmental delay, hypotonia, and muscle weakness. Consistently, patient-derived cells show fusion defects that can be fully rescued by restoring Myomaker expression. Structure and function analyses identify C2H2-type zinc-finger motifs on CHAMP1 protein that are both necessary and sufficient for MyoD interaction and Myomaker expression. These findings highlight a cell-autonomous role for CHAMP1 in muscle development and disease and point to therapeutic avenues for treating CHAMP1-related muscle development defects.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Life Sciences Research Foundation, National Institutes of Health, University of California, San Diego, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Congressionally Directed Medical Research Programs
Awards: Endoplasmic Reticulum-Targeted Radiodynamic Therapy for the Treatment of Lung Cancer, The development of novel radiation-sensitizer based on ultra-small carbon dots, G6067676908, Development of a novel biodegradable inorganic nanoparticle therapeutic for cancer, Discover the Boosters of Myoblast Fusion, G8466703706, Spatial genetics investigation of multinucleated cells
OpenAlex ID: W7124267311