Wang C, Song B
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago 60612, USA.
Mol Cell Biol. 1996 Feb;16(2):712-23. doi: 10.1128/MCB.16.2.712.
Platelet-derived growth factor alpha receptor (PDGF alpha R) is a transmembrane tyrosine kinase receptor for all three existing PDGF isoforms, AA, AB, and BB. Transcripts of PDGF alpha R are detected as early as in fertilized mouse eggs and throughout adulthood in a time- and space-specific manner, thereby suggesting an important role of PDGFs in mammalian development. In this study, we have investigated the mechanism involved in cell-type-specific PDGF alpha R gene expression during early embryonic development. Using F9 embryonic carcinoma cells as an in vitro study model, we identified a differentiation-dependent enhancer element within the PDGF alpha R promoter that controlled receptor expression during parietal endoderm cell differentiation induced by retinoic acid and dibutyryl cyclic AMP treatment. The differentiation-dependent enhancer element sequence bore no resemblance to consensus DNA-binding sites of either the retinoic acid receptor family or the cyclic AMP-responsive element-binding protein family. It was composed of two identical 12-bp direct repeats separated by a 17-bp insert sequence enriched in C and A nucleotides. Although only a single repeat was needed to form specific DNA-protein complexes with factors present in F9 parietal endoderm cell extracts, both repeats together were necessary to display cell-type-specific enhancing activity. Mutational analysis revealed that the protein-binding sites within the repeat sequences were identical to GATA-binding sites. In this study, we provided evidence to suggest that a member of the GATA transcription factor family (GATA-4) is responsible for parietal endoderm-specific PDGF alpha R expression.
血小板衍生生长因子α受体（PDGFαR）是所有三种现有PDGF亚型（AA、AB和BB）的跨膜酪氨酸激酶受体。PDGFαR的转录本早在受精的小鼠卵中就可检测到，并在成年期以时间和空间特异性的方式存在，这表明PDGF在哺乳动物发育中起重要作用。在本研究中，我们研究了早期胚胎发育过程中细胞类型特异性PDGFαR基因表达所涉及的机制。使用F9胚胎癌细胞作为体外研究模型，我们在PDGFαR启动子内鉴定出一个依赖分化的增强子元件，该元件在视黄酸和二丁酰环磷酸腺苷处理诱导的壁内胚层细胞分化过程中控制受体表达。依赖分化的增强子元件序列与视黄酸受体家族或环磷酸腺苷反应元件结合蛋白家族的共有DNA结合位点均无相似之处。它由两个相同的12个碱基对的直接重复序列组成，中间间隔一个富含C和A核苷酸的17个碱基对的插入序列。尽管只需要一个重复序列就能与F9壁内胚层细胞提取物中的因子形成特异性DNA-蛋白质复合物，但两个重复序列一起对于显示细胞类型特异性增强活性是必需的。突变分析表明，重复序列内的蛋白质结合位点与GATA结合位点相同。在本研究中，我们提供证据表明GATA转录因子家族的一个成员（GATA-4）负责壁内胚层特异性PDGFαR的表达。
