To further study these dichotomous potential outcomes of Wnt and RA signaling, we utilized CRISPR/Cas9 editing to remove the 27bp insertion from p300 gene of murine embryonal carcinoma (P19) cells and now demonstrate the effect on Stra6 expression and more generally stem cell differentiation and the critical nature of this region of p300 for β-catenin’s synergistic interaction with nuclear receptor. Here, STRA6 is linked to embryonal carcinoma.