Retinoic acid activates Hoxa4 chromatin

Stable Identifier
R-MMU-5619434
Type
Reaction [BlackBoxEvent]
Species
Mus musculus
Compartment
Summation

In mouse embryos retinoic acid initially activates expression of the Hoxa4 gene in rhombomere 7 (r7) and regions of mesoderm 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 (Behringer et al. 1993, Morrison et al. 1997, Packer et al. 1998, Packer et al. 2000), causing dissociation of corepressors and recruitment of corepressors (inferred from Hoxa1, Gillespie and Gudas 2007, Kashyap and Gudas 2010). Hoxa4 itself maintains later expression in an autoregulatory loop (Wu and Wolgemuth 1993, Packer et al. 1998).
Treatment of embryonic stem cells with retinoic acid causes loss of methylation at histone 3 lysine-27 (H3K27me3, Kashyap et al. 2011, Mazzoni et al. 2013, Shpargel et al. 2014), loss of Polycomb repressive complex 2 (PRC2, Mazzoni et al. 2013) and gain of methylation at histone 3 lysine-4 (H3K4me3, Kashyap et al. 2011) across the Hoxa gene cluster. The Mll2 complex methylates H3K4 at Hoxa4 in fibroblasts (Wang et al. 2009).

Literature References
PubMed ID Title Journal Year
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20231276 Epigenetic regulatory mechanisms distinguish retinoic acid-mediated transcriptional responses in stem cells and fibroblasts J. Biol. Chem. 2010
19703992 Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II Mol. Cell. Biol. 2009
21087926 Epigenomic reorganization of the clustered Hox genes in embryonic stem cells induced by retinoic acid J. Biol. Chem. 2011
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25101834 KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development PLoS Genet. 2014
9570764 Expression of the murine Hoxa4 gene requires both autoregulation and a conserved retinoic acid response element Development 1998
23955559 Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals Nat. Neurosci. 2013
8100763 Sequences 5' of the homeobox of the Hox-1.4 gene direct tissue-specific expression of lacZ during mouse development Development 1993
7901228 Protein product of the somatic-type transcript of the Hoxa-4 (Hox-1.4) gene binds to homeobox consensus binding sites in its promoter and intron J. Cell. Biochem. 1993
Participants
Orthologous Events