As inferred from mouse embryonic stem cells activated by retinoic acid (Kashyap et al. 2011, Mazzoni et al. 2013) and human cells, activation of chromatin at Hoxb3 is accompanied by loss of methylation at lysine-27 of histone H3 (H3K27me3, Kashyap et al. 2011, Mazzoni et al. 2013), loss of PRC2 (Mazzoni et al. 2013), and gain of methylation at H3K4 (Kashyap et al. 2011). The Mll2 complex methylates H3K4 at Hoxb3 in fibroblasts (Wang et al. 2009). In human cells the demethylase KDM6A (UTX) binds HOXB3 chromatin during activation and participates in demethylating H3K27me3.