Activation of enhancer elements by the homeobox gene Cdx2 is cell line specific.
Activation of enhancer elements by the homeobox gene Cdx2 is cell line specific.
复制标题
同源盒基因 Cdx2 对增强子元件的激活具有细胞系特异性。
DOI：
10.1093/nar/25.12.2293
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发表时间：
1997
影响因子：
14.9
通讯作者：
Traber,PG
中科院分区：
文献类型：
--
作者：
Taylor,JK;Levy,T;Suh,ER;Traber,PG
Cdx2是一种尾侧相关的同源域转录因子，在小鼠发育过程中以复杂的模式表达，并在成年小鼠的肠上皮中以高水平表达。Cdx2激活含有特异性结合位点的肠道基因启动子的转录。此外，Cdx2已显示在细胞系中诱导肠分化。在这项研究中，我们表明，Cdx2是能够结合到两个明确定义的增强子元件在HoxC8基因。然后，我们证明，Cdx2是能够激活异源启动子的转录时，其DNA结合元件被放置在一个增强子上下文。此外，激活增强子元件的能力依赖于细胞系。当Cdx2激活结构域连接到Gal4 DNA结合结构域时，嵌合蛋白能够激活肠细胞系中的Gal4增强子构建体，但不能激活NIH3T3细胞中的转录。这些数据表明，有细胞特异性因子，使Cdx2激活结构域的功能，在激活增强子元件。我们推测，无论是共激活蛋白或差异磷酸化的激活结构域可能是肠细胞系特异性功能的Cdx2的机制，并可能在其他组织的早期发展。
Cdx2 is a caudal-related homeodomain transcription factor that is expressed in complex patterns during mouse development and at high levels in the intestinal epithelium of adult mice. Cdx2 activates transcription of intestinal gene promoters containing specific binding sites. Moreover, Cdx2 has been shown to induce intestinal differentiation in cell lines. In this study, we show that Cdx2 is able to bind to two well defined enhancer elements in the HoxC8 gene. We then demonstrate that Cdx2 is able to activate transcription of heterologous promoters when its DNA binding element is placed in an enhancer context. Furthermore, the ability to activate enhancer elements is cell-line dependent. When the Cdx2 activation domain was linked to the Gal4 DNA binding domain, the chimeric protein was able to activate Gal4 enhancer constructs in an intestinal cell line, but was unable to activate transcription in NIH3T3 cells. These data suggest that there are cell-specific factors that allow the Cdx2 activation domain to function in the activation of enhancer elements. We hypothesize that either a co-activator protein or differential phosphorylation of the activation domain may be the mechanism for intestinal cell line-specific function of Cdx2 and possibly in other tissues in early development.