In human fibroblasts (Lan et al. 2007) and human embryonic carcinoma cells (Lee et al. 2007, Sessa et al. 2007) treated with retinoic acid HOXA3 chromatin is activated by loss of methylation at lysine-27 of histone H3 (H3K27me3) and gain of H3K4me3. KDM6A (UTX) binds near HOXA3 (Lan et al. 2007, Lee et al. 2007) but does not appear to participate in the loss of H3K27me3. KDM6A forms complexes with the histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 (Lee et al. 2007). Polycomb repressive complex 2 (PRC2), which binds H3K27me3, is also lost during activation of HOXA3 (Lan et al. 2007, Lee et al. 2007, Sessa et al. 2007). The change in chromatin at HOXA3 may result from euchromatin spreading from distant 3' retinoic acid response elements. The chromosomal conformation of the entire HOXA cluster changes during activation (Rousseau et al. 2014).
Xu, M, Zhao, GN, Lv, X, Liu, G, Wang, LY, Hao, DL, Wang, J, Liu, DP, Liang, CC
Rousseau, M, Crutchley, JL, Miura, H, Suderman, M, Blanchette, M, Dostie, J
Lan, F, Bayliss, PE, Rinn, JL, Whetstine, JR, Wang, JK, Chen, S, Iwase, S, Alpatov, R, Issaeva, I, Canaani, E, Roberts, TM, Chang, HY, Shi, Y
Sessa, L, Breiling, A, Lavorgna, G, Silvestri, L, Casari, G, Orlando, V
Lee, MG, Villa, R, Trojer, P, Norman, J, Yan, KP, Reinberg, D, Di Croce, L, Shiekhattar, R
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