De novo hydroxymethylated enhancers bind pioneer factors driving NPC commitment. (A) Average kinetic profiles of 5hmC, 5mC, H3K4me1, H3K27ac, and chromatin opening (FAIRE) at 20,492 regions gaining 5hmC (up-DhMRs) at 48 h of P19 ECC differentiation. (B) Average profiles of FOXA1, PBX1, and MEIS1 binding at up-DhMRs at 48 h of differentiation. (C) Heat map representations of 5hmC signal at MEIS1, PBX1, and FOXA1 enriched regions in 48 h RA-treated P19 cells.