As inferred from mouse embryonic stem cells activated by retinoic acid (Kashyap et al. 2011, Mazzoni et al. 2013) and human cell lines, methylation at lysine-27 of histone H3 (H3K27me3) is lost (Kashyap et al. 2011, Mazzoni et al. 2013), Polycomb repressive complex 2 (PRC2) is lost (Mazzoni et al. 2013), and methylation at lysine-4 (H3K4me3) is gained (Kashyap et al. 2011). The Mll2 complex methylates H3K4 at Hoxb2 in fibroblasts (Wang et al. 2009). In human cells, the histone demethylase KDM6A (UTX) binds HOXB2 chromatin and demethylates H3K27me3. Other factors may also participate in demethylation.