Porcine DUXC and human DUX4 activate similar embryonic programs cross species: implications for preclinical model of FSHD

DUX4 and its mouse ortholog Dux are normally expressed in the early embryo—the 4 cell or 2 cell cleavage stage embryo, respectively—and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas FSHD-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program, and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a pre-clinical model for FSHD. In this study, we identify the porcine DUXC mRNA expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD. Overexpression of human DUX4, pig DUXC, or GFP control in primary pig myoblasts.