A multiplicity of differentiation-regulated ATF site-binding activities in embryonal carcinoma cells with distinct sequence and promoter specificities

Abstract

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.