Retinoic acid induces expression of Hoxd3 in embryos (Folberg et al. 1999) and fetal cortical neurons (Chai et al. 2009), but it is unknown if the effect is direct or indirect. The retinoid receptor Rarb is not responsible for the inducibility in embryos (Folberg et al. 1999). Hoxd3 is expressed in rhombomeres 5,6, and 7 (r5-7) (Tan et al. 1996, Gaufo et al. 2003) and in more caudal regions: the spinal cord, dorsal root ganglia, first cervical vertebrae, thyroid gland, kidney tublules, esophagus, stomach, and intestines (Tan et al. 1996).
In mouse embryonic stem cells treated with retinoic acid Hoxd3 chromatin is activated by loss of methylation at lysine-27 of histone H3 (H3K27me3) and loss of Polycomb repressive complex 2 (PRC2) (Williamson et al. 2012, Mazzoni et al. 2013). In human fibroblasts, the histone demethylase KDM6A participates in removing H3K27me3. The Mll2 complex methylates H3K4 at Hoxd3 in fibroblasts (Wang et al. 2009).