The PRC2-associated factor EPOP is required for Hox gene regulation during axial development in mice

The Polycomb repressive complex 2 (PRC2) is an essential modulator of gene repression. We previously reported that, in mouse embryonic stem cells, PRC2 associates with elonginB/C through EPOP, which allows for low-level expression of target genes. Here we investigate the role of EPOP in vivo by generating a mouse knockout (KO) model. We show that Epop KO mice are viable and fertile but display highly penetrant posterior homeotic transformations of the axial skeleton, which can be partially recapitulated by deletion of only the maternal allele. Epop-depleted embryos present a shift of the anterior boundary of expression of certain Hox genes. Tissue-specific RNA sequencing of embryos suggests that the Hox activation defect originates at the level of the presomitic mesoderm. Overall, we find that EPOP prevents premature activation of a subset of Hox genes, and that this is required for correct body patterning along the antero-posterior axis.