Reactome | Retinoic acid activates Hoxb4 chromatin

Retinoic acid activates Hoxb4 chromatin

Stable Identifier

R-MMU-5619411

Type

Reaction [omitted]

Species

Mus musculus

Compartment

nucleoplasm

ReviewStatus

5/5

General

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Retinoic acid activates the Hoxb4 gene in rhombomere 7 (r7) by binding the retinoic acid receptor Rarb (Folberg et al. 1999) and perhaps Rara in Rar:Rxr dimers bound to retinoic acid response elements (RAREs) located in the 3' flanking region of the Hoxb4 gene (Morrison et al. 1997, Gould et al. 1998), causing dissociation of corepressors and recruitment of coactivators (inferred from Hoxa1, Gillespie and Gudas 2007, Kashyap and Gudas 2010). Hoxb4 maintains its own expression by binding and activating its own promoter (Gould et al. 1997, Serpente et al. 2005).
In embryonic stem cells treated with retinoic acid (Kashyap et al. 2011, Mazzoni et al. 2013) and in human cells, activation of chromatin at the Hoxb4 gene is due to loss of methylation of lysine-27 at histone H3 (H3K27me3, Kashyap et al. 2011, Mazzoni et al. 2013), loss of Polycomb repressive complex 2 (PRC2, Mazzoni et al. 2013), and gain of H3K4me3 (Kashyap et al. 2011). The Mll1 and Mll2 complexes methylate H3K4 at Hoxb4 in fibroblasts (Wang et al. 2009). In human cells the histone demethylase KDM6A (UTX) binds the HOXB4 gene and participates in demethylating H3K27me3. Other factors may be involved in demethylation (Shpargel et al. 2014).

Literature References

PubMed ID	Title	Journal	Year
9272954	HOXD4 and regulation of the group 4 paralog genes Krumlauf, R, Featherstone, M, Morrison, A, Gould, A, Ariza-McNaughton, L	Development	1997
9106661	Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns Krumlauf, R, Morrison, A, Gould, A, White, RA, Sproat, G	Genes Dev.	1997
17663992	Retinoid regulated association of transcriptional co-regulators and the polycomb group protein SUZ12 with the retinoic acid response elements of Hoxa1, RARbeta(2), and Cyp26A1 in F9 embryonal carcinoma cells Gudas, LJ, Gillespie, RF	J. Mol. Biol.	2007
20231276	Epigenetic regulatory mechanisms distinguish retinoic acid-mediated transcriptional responses in stem cells and fibroblasts Kashyap, V, Gudas, LJ	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 Ge, K, Gogol, M, Wiedemann, LM, Seidel, C, Guo, H, Smith, ER, Alexander, T, Sanderson, BW, Lin, C, Wang, P, Wu, M, Shilatifard, A, Krumlauf, R	Mol. Cell. Biol.	2009
21087926	Epigenomic reorganization of the clustered Hox genes in embryonic stem cells induced by retinoic acid Kashyap, V, Brenet, F, Viale, A, Funk, P, Gudas, LJ, Scandura, JM	J. Biol. Chem.	2011
9697850	Initiation of rhombomeric Hoxb4 expression requires induction by somites and a retinoid pathway Krumlauf, R, Gould, A, Itasaki, N	Neuron	1998
15634700	Direct crossregulation between retinoic acid receptor {beta} and Hox genes during hindbrain segmentation Gould, AP, Chambon, P, Wiedemann, LM, Serpente, P, Ghyselinck, NB, Tümpel, S, Niederreither, K, Krumlauf, R, Dollé, P	Development	2005
25101834	KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development Starmer, J, Pohlers, M, Yee, D, Shpargel, KB, Magnuson, T	PLoS Genet.	2014
10373014	RARbeta mediates the response of Hoxd4 and Hoxb4 to exogenous retinoic acid Featherstone, MS, Giguère, V, Folberg, A, Nagy Kovács, E, Luo, J	Dev. Dyn.	1999
23955559	Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals Boyer, LA, Thornton, SR, Gifford, DK, Young, RA, McCuine, S, Mazzoni, EO, Patel, T, Peljto, M, Wichterle, H, Reeder, C, Mahony, S	Nat. Neurosci.	2013

Participants

Input

Output

Orthologous Events

Retinoic acid activates HOXB4 chromatin (Homo sapiens)

Authored

May, B (2014-08-16)

Rezsohazy, R (2015-11-15)

Reviewed

Blasi, F (2015-05-13)

Created

May, B (2014-08-22)