TRANSCRIPTION FACTOR AP2 AND ITS ROLE IN EPIDERMAL-SPECIFIC GENE-EXPRESSION
TRANSCRIPTION FACTOR AP2 AND ITS ROLE IN EPIDERMAL-SPECIFIC GENE-EXPRESSION
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DOI：
10.1073/pnas.88.18.7948
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发表时间：
1991-09-01
影响因子：
11.1
通讯作者：
FUCHS, E
中科院分区：
文献类型：
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作者：
LEASK, A;BYRNE, C;FUCHS, E
表皮是复层鳞状上皮，其主要分化特异性产物是角蛋白。为了阐明控制角质形成细胞特异性基因表达的因素，我们以前确定了近端和远端调控元件，协同作用，以驱动编码人表皮角蛋白K14的基因的角质形成细胞特异性表达。近端元件的控制是由转录因子KERI介导的，KERI在角质形成细胞的核提取物中比在其他细胞类型的提取物中更丰富，包括成纤维细胞、淋巴细胞和简单的上皮细胞。在这份报告中，我们确定这个因子作为转录因子AP2，显示在表皮和神经嵴谱系的细胞中转录。此外，我们证明了三个额外的表皮基因上游的功能性AP2结合位点，这表明AP2通常可能参与表皮基因调控。最后，虽然AP 2是必要的，但它不足以表皮基因表达：远端元件有助于人角蛋白K14基因的组织特异性表达，这是通过其在角质形成细胞中增强异源启动子表达的能力而不是在肝癌细胞中来判断的。这些结果表明，一个因素的组合可能有助于表皮特异性表达的人角蛋白K14基因。
The epidermis is a stratified squamous epithelium whose major differentiation-specific products are keratins. To elucidate factors controlling keratinocyte-specific gene expression, we previously identified proximal and distal regulatory elements that act synergistically to drive keratinocyte-specific expression of the gene encoding human epidermal keratin K14. Control by the proximal element is mediated by a transcription factor, KERI, which is more abundant in nuclear extracts of keratinocytes than in extracts of other cell types, including fibroblasts, lymphocytes, and simple epithelial cells. In this report, we identify this factor as transcription factor AP2, shown to be transcribed in cells of epidermal and neural crest lineages. Furthermore, we demonstrate functional AP2 binding sites upstream from three additional epidermal genes, suggesting that AP2 may be generally involved in epidermal gene regulation. Finally, although AP2 is necessary, it is not sufficient for epidermal gene expression: a distal element contributes to tissue-specific expression of the human keratin K14 gene as judged by its ability to enhance expression of a heterologous promoter in keratinocytes but not in hepatoma cells. These results imply that a combination of factors is likely to contribute to epidermal-specific expression of the human keratin K14 gene.