HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: Formation of multimeric complexes on HOXA10 target genes
HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: Formation of multimeric complexes on HOXA10 target genes
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DOI：
10.1210/jc.2004-0817
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发表时间：
2005-01-01
影响因子：
5.8
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Sarno, JL;Kliman, HJ;Taylor, HS
HOXA 10是胚胎子宫发育和成人子宫内膜容受性所必需的转录因子。辅因子的三个氨基酸环延伸家族，包括Pbx和Meis，在发育和髓样分化中提供HOX靶基因特异性。在这里，我们展示了Pbx和Meis家族辅因子在人类子宫内膜中的表达及其与HOXA 10的相互作用。利用免疫组化分析，我们发现，Pbx 2和Meis 1，但没有Pbx 1，Pbx 3，或Meis 2，表达在人子宫内膜。HOXA 10，Pbx 2和Meis 1在整个月经周期中在基质中表达。HOXA 10和Meis 1的腺体表达是月经周期阶段特异性的，而腺体Pbx 2表达没有变化。Pbx 2在石川细胞中表达，而Meis 1不表达。EMSA证明HOXA 10-Pbx 2作为异二聚体结合到EMX 2基因的增强子，EMX 2基因是HOXA 10调节的已知靶点。消融的Pbx结合位点，但不消融的HOXA 10结合位点的EMX 2，导致损失的二聚体结合。基于观察到的Pbx 2、Meis 1和HOXA 10的表达和结合模式，很可能涉及这些蛋白质的异二聚体和三聚体复合物决定HOXA 10靶基因特异性。通过多聚体结合增强靶基因特异性可能是HOXA 10介导的子宫内膜容受性所必需的。
HOXA10 is a transcription factor necessary for embryonic uterine development and for adult endometrial receptivity. The three-amino acid loop extension family of cofactors, including Pbx and Meis, provide HOX target gene specificity in development and myeloid differentiation. Here we demonstrate the expression of Pbx and Meis family cofactors in the human endometrium and their interaction with HOXA10. Using immunohistochemical analysis, we found that Pbx2 and Meis1, but not Pbx1, Pbx3, or Meis2, were expressed in human endometrium. HOXA10, Pbx2, and Meis1 were expressed in the stroma throughout the menstrual cycle. The glandular expression of HOXA10 and Meis1 was menstrual cycle stage specific, whereas glandular Pbx2 expression did not vary. Pbx2, but not Meis1, was expressed in Ishikawa cells. EMSA demonstrated HOXA10-Pbx2 binding as a heterodimer to an enhancer of the EMX2 gene, a known target of HOXA10 regulation. Ablation of the Pbx binding site, but not ablation of the HOXA10 binding site in EMX2, resulted in loss of dimer binding. Based on the observed expression and binding patterns of Pbx2, Meis1, and HOXA10, it is likely that heterodimeric and trimeric complexes involving these proteins determine HOXA10 target gene specificity. Enhanced target gene specificity imparted by multimer binding is likely necessary for HOXA10-mediated endometrial receptivity.