The PRC2 associated factor Epop is required for Hox genes 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 (mESCs), PRC2 associates with ElonginB/C through EPOP, allowing for low-level expression of target genes. Here we investigate the role of Epop in vivo by generating a mouse knockout model: we show that Epop null mice are viable and fertile, but display highly penetrant posterior homeotic transformations of the axial skeleton. Consistently, Epop depleted embryos present a shift of the anterior boundary of expression of certain Hox genes. Tissue-specific RNA-seq in embryos suggest that the defect in Hox activation originates already at the level of the presomitic mesoderm (PSM). Overall, our findings indicate that Epop is specifically required for correct body patterning along the antero-posterior axis, by preventing premature activation of the Hox genes. Overall design: 8 paired-end RNA-seq experiments from the posterior part of the tailbud of 4-5 somite-matched E8.5 embryos(WT means wild-type, KO means EPOP KO)