RNA-seq analysis of global gene expression changes in human FSHD immortalized myotubes following treatment with the BAZ1A inhibitor C06

Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic dysregulation of the disease locus, leading to pathogenic misexpression of DUX4 in skeletal muscle. We identified BAZ1A (bromodomain adjacent to zinc finger domain protein 1A) as a promising target for FSHD therapeutic development, and identified a small-molecule compound termed C06 that binds BAZ1A in vitro and is a potent repressor of DUX4. To determine the global specificity of C06 activity, we performed RNA-seq on FSHD myotubes treated with different concentrations of C06, and compared the gene expression profiles. At low concentrations, C06 returns the DUX4 gene expression signature to a healthier profile without major effects on the muscle transcriptome. Thus, C06 is a useful tool for potent and specific DUX4 suppression, and a viable candidate for further development.