Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity.

摘要: The Xenopus vitellogenin (vit) gene B1 estrogen-inducible enhancer is formed by two closely adjacent 13 bp imperfect palindromic estrogen-responsive elements (EREs), i.e. ERE-2 and ERE-1, having one base substitutions respectively, when compared to the perfect consensus ERE (GGTCANNNTGACC). Gene transfer experiments indicate that these degenerated elements, on their own, have a low or no regulatory capacity at all, but in vivo act together synergistically confer high receptor- hormone-dependent transcription activation heterologous HSV thymidine kinase promoter. Thus, DNA region upstream of vitB1 comprising EREs separated 7 bp, was called unit (vitB1 ERU). Using vitro protein-DNA interaction techniques, we demonstrate estrogen receptor dimers bind cooperatively ERU. Binding first dimer more conserved increases approximately 4- 8-fold binding affinity less ERE-1. suggest observed synergistic estrogen-dependent conferred pair hormone-responsive vit ERU result cooperative EREs.