Foxp2 inhibits Nkx2.1-mediated transcription of SP-C via interactions with the Nkx2.1 homeodomain.
Foxp2 inhibits Nkx2.1-mediated transcription of SP-C via interactions with the Nkx2.1 homeodomain.
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Foxp2 通过与 Nkx2.1 同源域相互作用抑制 Nkx2.1 介导的 SP-C 转录。
DOI：
10.1165/rcmb.2007-0350oc
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发表时间：
2008
影响因子：
6.4
通讯作者：
Borok,Zea
中科院分区：
文献类型：
--
作者：
Zhou,Beiyun;Zhong,Qian;Minoo,Parviz;Li,Changgong;Ann,DavidK;Frenkel,Baruch;Morrisey,EdwardE;Crandall,EdwardD;Borok,Zea
转录因子（TF）Foxp 2已被证明部分抑制表面活性蛋白C（SP-C）转录，推测是通过SP-C启动子中的独立阻遏物结构域与保守Foxp 2共有位点的相互作用。我们探讨了Foxp 2和同源域TF Nkx2.1之间的相互作用的作用，这可能有助于显着减少SP-C表达伴随肺泡上皮II型（AT 2）的表型转变为I型（AT 1）细胞。Foxp 2剂量依赖性地抑制MLE-15细胞中Nkx2.1介导的SP-C活化。虽然电泳迁移率变动分析和染色质免疫沉淀揭示了Foxp 2和SP-C启动子中保守的共有基序之间的相互作用，但Nkx2.1介导的318 bp近端SP-C启动子（缺乏Foxp 2共有基序）的激活通过增加Foxp 2的量而减弱。免疫共沉淀和哺乳动物双杂交试验证实了Nkx2.1和Foxp 2之间通过Nkx2.1同源结构域介导的物理相互作用。Nkx2.1与SP-C寡核苷酸复合物的形成被重组Foxp 2剂量依赖性地抑制。这些发现表明，Foxp 2和Nkx2.1之间的直接相互作用抑制Nkx2.1 DNA结合和转录活性，并建议在AT 2细胞向AT 1细胞表型转变过程中下调SP-C（可能还有其他AT 2细胞基因）的机制。
The transcription factor (TF) Foxp2 has been shown to partially repress surfactant protein C (SP-C) transcription, presumably through interaction of an independent repressor domain with a conserved Foxp2 consensus site in the SP-C promoter. We explored the role of interactions between Foxp2 and the homeodomain TF Nkx2.1 that may contribute to the marked reduction in SP-C expression accompanying phenotypic transition of alveolar epithelial type II (AT2) to type I (AT1) cells. Foxp2 dose-dependently inhibited Nkx2.1-mediated activation of SP-C in MLE-15 cells. While electrophoretic mobility shift assays and chromatin immunoprecipitations revealed an interaction between Foxp2 and the conserved consensus motif in the SP-C promoter, Nkx2.1-mediated activation of the 318-bp proximal SP-C promoter (which lacks a Foxp2 consensus) was attenuated by increasing amounts of Foxp2. Co-immunoprecipitation and mammalian two-hybrid assays confirmed a physical interaction between Nkx2.1 and Foxp2 mediated through the Nkx2.1 homeodomain. Formation of an Nkx2.1 complex with an SP-C oligonucleotide was inhibited dose-dependently by recombinant Foxp2. These findings demonstrate that direct interaction between Foxp2 and Nkx2.1 inhibits Nkx2.1 DNA-binding and transcriptional activity and suggest a mechanism for down-regulation of SP-C (and probably other AT2 cell genes) during transition of AT2 cells to an AT1 cell phenotype.
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DOI：
--
发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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DOI：
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DOI：
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发表时间：
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影响因子：
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