PIAS1,3 SUMOylates MBD1 at lysine-499 and lysine-538 of the reference sequence (lysine-450 and lysine-489 of isoform 5) with SUMO1 (Uchimura et al. 2006, Hendriks et al. 2014, Hendriks et al. 2017, Breuker and Pichler 2019). SUMOylation of MBD1 enhances its interaction with MCAF1 (Uchimura et al. 2006).

In human cell lines and tissues activation of HOXA2 chromatin by retinoic acid occurs through loss of methylation at lysine-27 of histone H3 (H3K27), dissociation of polycomb repressive complexes, and gain of methylation at H3K4 (Lee et al. 2007 Supplementary, Sakamoto et al. 2007, Sessa et al. 2007). The change in chromatin may be produced by euchromatin spreading from distant 3' retinoic acid response elements. DNA methylation and MBD1 also appear to play a role in maintaining repression at HOXA2 in HeLa cells (Sakamoto et al. 2007). The histone demethylase KDM6A binds HOXA2 (Lee et al. 2007 Supplementary) and may participate in removing H3K27 methylation. KDM6A associates with histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 in embryonal carcinoma cells (Lee et al. 2007, also observed at other HOXA genes in Lan et al. 2007). The conformation of the entire HOXA cluster in the nucleus changes during differentiation of a myeloid leukemia cell line and the conformation changes correlate with gene activity, H3K27me2,3 occurence, and proximity to CTCF binding sites (Rousseau et al. 2014, see also Lonfat and Duboule 2015).