Retinoic acid activates HOXA4 chromatin

Stable Identifier
Reaction [omitted]
Homo sapiens
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As inferred from mouse embryos, retinoic acid initially activates expression of the HOXA4 gene in rhombomere 7 (r7) by binding RARB or RARA in dimeric RAR:RXR complexes located at retinoic acid response elements (RAREs) in the 5' flanking region of the HOXA4 promoter (also observed in human teratocarcinoma cells in Doerksen et al. 1996, Sessa et al. 2007), correlating dissociation of corepressors and recruitment of coactivators. In mouse embryos Hoxa4 itself maintains later expression in an autoregulatory loop.
In human fibroblasts (Lan et al. 2007) and teratocarcinoma cells (Sessa et al 2007) activation of HOXA4 chromatin is accompanied by loss of methylation at lysine-27 of histone H3 (H3K27me3) and gain of H3K4me3. The polycomb repressive complex 2 (PRC2), which binds H3K27me3, is also reduced at active HOXA4 chromatin (Lan et al. 2007, Sessa et al. 2007).
Literature References
PubMed ID Title Journal Year
24174538 Hox in motion: tracking HoxA cluster conformation during differentiation

Crutchley, JL, Blanchette, M, Rousseau, M, Suderman, M, Dostie, J, Miura, H

Nucleic Acids Res. 2014
25135475 CTCF Controls HOXA Cluster Silencing and Mediates PRC2-Repressive Higher-Order Chromatin Structure in NT2/D1 Cells

Wang, J, Lv, X, Liu, G, Liang, CC, Zhao, GN, Xu, M, Liu, DP, Hao, DL, Wang, LY

Mol. Cell. Biol. 2014
17851529 A histone H3 lysine 27 demethylase regulates animal posterior development

Rinn, JL, Wang, JK, Lan, F, Shi, Y, Issaeva, I, Chang, HY, Whetstine, JR, Alpatov, R, Iwase, S, Chen, S, Bayliss, PE, Roberts, TM, Canaani, E

Nature 2007
17185360 Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster

Casari, G, Sessa, L, Breiling, A, Silvestri, L, Orlando, V, Lavorgna, G

RNA 2007
8759021 Functional interaction between a RARE and an AP-2 binding site in the regulation of the human HOX A4 gene promoter

Kannan, P, Doerksen, LF, Pratt, D, Tainsky, MA, Bhattacharya, A

Nucleic Acids Res. 1996
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