As inferred from mouse embryonic stem cells (Kashyap et al. 2011, Mazzoni et al. 2013) and embryos (Diman et al. 2011) activated by retinoic acid and human fibroblasts and embryonal carcinoma cells, Hoxa3 chromatin is activated by loss of methylation at lysine-27 of histone H3 (H3K27me3, Kashyap et al. 2011, Mazzoni et al. 2013). loss of Polycomb repressive complex (PRC2, Mazzoni et al. 2013), and gain of H3K4me3 (Kashyap et al. 2011). The Mll2 complex methylates H3K4 at Hoxa3 in fibroblasts (Wang et al. 2009). In human cells KDM6A (UTX) binds HOXA3 and participates in the loss of H3K27me3.