ANALYSIS OF ESTROGEN-RECEPTOR INTERACTION WITH TERTIARY-STRUCTURED ESTROGEN RESPONSIVE ELEMENTS

An initial crucial step in estrogen activation of gene expression is t he interaction of the estrogen receptor with a specific nucleotide seq uence [estrogen responsive element (ERE)]. Previously, we found that t he estrogen receptor binds preferentially and with high affinity to th e lower strand of the rat prolactin imperfect ERE which contains terti ary structure (Lannigan DA and Notides AC, Proc Natl Acad Sci USA 86: 863-867, 1989). Using perfect and imperfect EREs from the upstream reg ion of the chicken vitellogenin II gene, we have now extended our find ings and have determined that the estrogen receptor preferentially int eracts with either perfect or imperfect EREs which contain tertiary st ructure. A similar structure is present in a synthetic 42 bp oligonucl eotide corresponding to the lower strand of a perfect ERE with flankin g sequences from the rat prolactin ERE. Moreover, deviations from the ERE consensus sequence decrease the binding of the estrogen receptor t o the tertiary-structured ERE. We also have determined that ERE flanki ng sequences contribute to the affinity of the receptor for the tertia ry-structured ERE. Furthermore, ERE flanking sequences can influence t he types of interactions that the estrogen receptor makes with the ter tiary-structured ERE.