Positive and negative regulation of the transforming growth factor β/activin target gene goosecoid by the TFII-I family of transcription factors
Positive and negative regulation of the transforming growth factor β/activin target gene goosecoid by the TFII-I family of transcription factors
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DOI：
10.1128/mcb.25.16.7144-7157.2005
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Hata, A
中科院分区：
文献类型：
--
作者：
Ku, MC;Sokol, SY;Hata, A
Goosecoid（Gsc）是一种存在于多种脊椎动物物种中的含有同源结构域的转录因子，并且已知其调节胚胎的形成和图案化。在这里，我们表明，在胚胎癌P19细胞中，转录因子TFII-I形成一个复合物与Smad 2后，转化生长因子β（TGF β）/激活素刺激，募集到远端元件（DE）的GSC启动子，并激活GSC转录。在P19细胞中通过小抑制性RNA下调内源性TFII-I消除了TGF β介导的Gsc诱导。同样，通过注射TFII-I特异性反义寡核苷酸下调内源性TFII-I表达的爪蟾胚胎表现出Gsc表达降低。与TFII-I不同，相关因子BEN（早期增强子结合因子）在不存在TGF β/激活素信号传导的情况下组成性募集至远端元件，并且在TGF β/激活素刺激时被TFII-I/Smad 2复合物取代。BEN在P19细胞中的过表达抑制TGF β介导的Gsc转录激活。这些结果提示了一种模型，其中TFII-I家族蛋白在响应TGF β/激活素的Gsc基因调节中具有相反的作用。
Goosecoid (Gsc) is a homeodomain-containing transcription factor present in a wide variety of vertebrate species and known to regulate formation and patterning of embryos. Here we show that in embryonic carcinoma P19 cells, the transcription factor TFII-I forms a complex with Smad2 upon transforming growth factor beta (TGF beta)/activin stimulation, is recruited to the distal element (DE) of the Gsc promoter, and activates Gsc transcription. Downregulation of endogenous TFII-I by small inhibitory RNA in P19 cells abolishes the TGF beta-mediated induction of Gsc. Similarly, Xenopus embryos with endogenous TFII-I expression downregulated by injection of TFII-I-specitic antisense oligonucleotides exhibit decreased Gsc expression. Unlike TFII-I, the related factor BEN (binding factor for early enhancer) is constitutively recruited to the distal element in the absence of TGF beta/activin signaling and is replaced by the TFII-I/Smad2 complex upon TGF beta/activin stimulation. Overexpression of BEN in P19 cells represses the TGF beta-mediated transcriptional activation of Gsc. These results suggest a model in which TFII-I family proteins have opposing effects in the regulation of the Gsc gene in response to a TGF beta/activin