Tassios P T, La Thangue N B
Laboratory of Eukaryotic Molecular Genetics, National Institute for Medical Research, Mill Hill, London, UK.
New Biol. 1990 Dec;2(12):1123-34.
Cells of the F9 murine embryonal carcinoma (F9 EC) line have an activity that stimulates transcription from early adenovirus gene promoters. One such promoter, that of the E4 gene, is transcribed efficiently in F9 EC cells and is activated further as these cells differentiate to parietal endoderm-like cells (F9 PE). The sequences required for this in vivo regulation include the activating transcription factor (ATF)-binding site, and consistent with this we show that complexes formed on this site are regulated as F9 EC cells differentiate. Another ATF site-containing promoter is that of the human vasoactive intestinal polypeptide (VIP). In contrast to the E4 promoter, the VIP promoter is transcriptionally inactive throughout differentiation, a feature that correlates with distinct binding activities on its ATF site. We define five ATF site-binding activities in F9 cells that can be distinguished from each other by their precise sequence requirements and their regulation during differentiation. From these activities, we define those that bind in a promoter-specific or promoter-common fashion to the E4 and VIP promoters. These data indicate that members of the ATF family of transcription factors are differentiation-regulated and support the idea that they provide diverse transcriptional stimuli.
F9小鼠胚胎癌细胞系的细胞具有刺激腺病毒早期基因启动子转录的活性。其中一个这样的启动子，即E4基因的启动子，在F9胚胎癌细胞中能高效转录，并且随着这些细胞分化为滋养层内胚层样细胞（F9 PE），其转录活性进一步增强。这种体内调控所需的序列包括激活转录因子（ATF）结合位点，与此一致的是，我们发现随着F9胚胎癌细胞的分化，在该位点形成的复合物也受到调控。另一个含有ATF位点的启动子是人类血管活性肠肽（VIP）的启动子。与E4启动子不同，VIP启动子在整个分化过程中转录无活性，这一特征与其ATF位点上不同的结合活性相关。我们在F9细胞中定义了五种ATF位点结合活性，它们可以通过其精确的序列要求以及在分化过程中的调控来相互区分。从这些活性中，我们确定了那些以启动子特异性或启动子共有的方式与E4和VIP启动子结合的活性。这些数据表明，ATF转录因子家族成员受分化调控，并支持它们提供多种转录刺激的观点。
