As inferred from mouse embryonic stem cells activated by retinoic acid (Kashyap et al. 2011, Mazzoni et al. 2013, Shpargel et al. 2014) and human cell lines, activation of Hoxa2 chromatin is accompanied by loss of methylation at lysine-27 of histone H3 (H3K27, Kashyap et al. 2011, Mazzoni et al. 2013, Shpargel et al. 2014), dissociation of polycomb repressive complexes (Mazzoni et al. 2013), and gain of methylation at H3K4 (Kashyap et al. 2011). The histone demethylase Kdm6a and possibly other factors (Shpargel et al. 2014) may participate in removing H3K27 methylation. The Mll2 complex methylates H3K4 at Hoxa2 in fibroblasts (Wang et al. 2009).