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Publication : Transient activation of meox1 is an early component of the gene regulatory network downstream of hoxa2.

First Author  Kirilenko P Year  2011
Journal  Mol Cell Biol Volume  31
Issue  6 Pages  1301-8
PubMed ID  21245383 Mgi Jnum  J:170613
Mgi Id  MGI:4946978 Doi  10.1128/MCB.00705-10
Citation  Kirilenko P, et al. (2011) Transient activation of meox1 is an early component of the gene regulatory network downstream of hoxa2. Mol Cell Biol 31(6):1301-8
abstractText  Hox genes encode transcription factors that regulate morphogenesis in all animals with bilateral symmetry. Although Hox genes have been extensively studied, their molecular function is not clear in vertebrates, and only a limited number of genes regulated by Hox transcription factors have been identified. Hoxa2 is required for correct development of the second branchial arch, its major domain of expression. We now show that Meox1 is genetically downstream from Hoxa2 and is a direct target. Meox1 expression is downregulated in the second arch of Hoxa2 mouse mutant embryos. In chromatin immunoprecipitation (ChIP), Hoxa2 binds to the Meox1 proximal promoter. Two highly conserved binding sites contained in this sequence are required for Hoxa2-dependent activation of the Meox1 promoter. Remarkably, in the absence of Meox1 and its close homolog Meox2, the second branchial arch develops abnormally and two of the three skeletal elements patterned by Hoxa2 are malformed. Finally, we show that Meox1 can specifically bind the DNA sequences recognized by Hoxa2 on its functional target genes. These results provide new insight into the Hoxa2 regulatory network that controls branchial arch identity.
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