Program in Gene Function and Expression; Program in Molecular Medicine
Adenovirus E1A Proteins; Animals; Base Sequence; Binding Sites; Carrier Proteins; Chloramphenicol O-Acetyltransferase; Cyclic AMP Response Element-Binding Protein; Embryonal Carcinoma Stem Cells; Gene Expression; Mice; Molecular Sequence Data; Neoplastic Stem Cells; *Promoter Regions, Genetic; Receptors, Retinoic Acid; Recombinant Fusion Proteins; Transfection; Tretinoin; Tumor Cells, Cultured
Genetics and Genomics
The retinoic acid (RA) receptor (RAR) beta 2 promoter is strongly activated by RA in embryonal carcinoma (EC) cells. We examined this activation in the P19 EC-derived END-2 cell line and in E1A-expressing counterparts and found strong RA-dependent RAR beta 2 promoter activation in the E1A-expressing cells, which was not observed in the parental cell line, indicating a possible role for E1A in RAR beta 2 activation. In transient transfection assays, E1A functioned as a coactivator of RA-dependent RAR beta 2 promoter activation and, moreover, was able to restore this activation in cells lacking RAR beta 2 activation. By deletion analysis, two regions in the RAR beta 2 promoter were identified that mediate the stimulatory effect of E1A: the RA response element and TATA box-containing region and a more up-stream region between -180 and -63, in which a cAMP response element-related motif was identified as a target element for E1A. In addition, determination of endogenous E1A-like activity by measuring E2A promoter activity in transient transfection assays in EC and differentiated cells revealed a correlation between RA-dependent RAR beta 2 promoter activation and the presence of this activity, suggesting an important role for the cellular equivalent of E1A in regulation of the RAR beta 2 promoter.
Mol Endocrinol. 1993 Apr;7(4):604-15. Link to article on publisher's site
Molecular endocrinology (Baltimore, Md.)
Kruyt, Frank A. E.; Folkers, Gert E.; Walhout, Albertha J. M.; van der Leede, Bas-jan M.; and van der Saag, Paul T., "E1A functions as a coactivator of retinoic acid-dependent retinoic acid receptor-beta 2 promoter activation" (1993). Program in Gene Function and Expression Publications and Presentations. 6.