A hox-eya-pax complex regulates early kidney developmental gene expression
A hox-eya-pax complex regulates early kidney developmental gene expression
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DOI：
10.1128/mcb.00465-07
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发表时间：
2007-11-01
影响因子：
5.3
通讯作者：
Wellik, Deneen M.
中科院分区：
文献类型：
--
作者：
Gong, Ke-Qin;Yallowitz, Alisha R.;Wellik, Deneen M.
在胚胎发育过程中，前后体轴部分是由Hox基因的组合活动决定的。鉴于Hox蛋白的DNA结合特异性较差，它们与辅助因子相互作用以调节靶基因是至关重要的。然而，很少有调控伙伴或下游靶基因被确定。在此，我们证明了Hox11的旁系蛋白与Pax2和Eya1形成复合物，直接激活后肾间质中Six2和Gdnf的表达。我们已经确定了Six2增强子中hox11 - eya1 - pax2介导激活所必需的结合位点，并证明该位点对Six2在体内的表达至关重要。此外，Hox11和Eya1之间的遗传相互作用与它们参与同一途径一致。因此，前后模式的Hox蛋白与肾源性中胚层规范的重要因子Pax2和Eya1相互作用，直接调节早期肾脏发育过程中下游靶基因的激活。
During embryonic development, the anterior-posterior body axis is specified in part by the combinatorial activities of Hox genes. Given the poor DNA binding specificity of Hox proteins, their interaction with cofactors to regulate target genes is critical. However, few regulatory partners or downstream target genes have been identified. Herein, we demonstrate that Hox11 paralogous proteins form a complex with Pax2 and Eya1 to directly activate expression of Six2 and Gdnf in the metanephric mesenchyme. We have identified the binding site within the Six2 enhancer necessary for Hox11-Eya1-Pax2-mediated activation and demonstrate that this site is essential for Six2 expression in vivo. Furthermore, genetic interactions between Hox11 and Eya1 are consistent with their participation in the same pathway. Thus, anterior-posterior-patterning Hox proteins interact with Pax2 and Eya1, factors important for nephrogenic mesoderm specification, to directly regulate the activation of downstream target genes during early kidney development.