HOXA2 chromatin is activated

Stable Identifier
R-HSA-6810139
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
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Summation

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).

Literature References
PubMed ID Title Journal Year
17428788 Overlapping roles of the methylated DNA-binding protein MBD1 and polycomb group proteins in transcriptional repression of HOXA genes and heterochromatin foci formation

Sakamoto, Y, Watanabe, S, Ichimura, T, Kawasuji, M, Koseki, H, Baba, H, Nakao, M

J. Biol. Chem. 2007
24174538 Hox in motion: tracking HoxA cluster conformation during differentiation

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

Nucleic Acids Res. 2014
25913784 Structure, function and evolution of topologically associating domains (TADs) at HOX loci

Lonfat, N, Duboule, D

FEBS Lett. 2015
17185360 Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster

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

RNA 2007
17761849 Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination

Lee, MG, Villa, R, Trojer, P, Norman, J, Yan, KP, Reinberg, D, Di Croce, L, Shiekhattar, R

Science 2007
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