SEQUENCE REQUIREMENTS FOR ESTROGEN-RECEPTOR BINDING TO ESTROGEN RESPONSE ELEMENTS

The estrogen receptor (ER) is a transcription factor that binds to a s pecific DNA sequence found in the regulatory regions of estrogen-respo nsive genes, called the estrogen response element (ERE), Many genes th at contain EREs have been identified, and most of these EREs contain o ne or more changes from the core consensus sequence, a 13-nucleotide s egment with 10 nucleotides forming an inverted repeat, A number of gen es have multiple copies of these imperfect EREs, In order to understan d why natural EREs have developed in this manner, we have attempted to define the basic sequence requirements for ER binding. To this end, w e measured the binding of homodimeric ER to a variety of nonconsensus EREs, We discovered that an ERE containing even a single change from t he consensus may be unable to bind ER, However, an ERE with two change s from the consensus may be capable of binding avidly to ER in the con text of certain flanking sequences. We found that changes in the seque nces flanking a nonconsensus ERE can greatly alter ER-ERE affinity, ei ther positively or negatively. Careful study of sequences flanking a s eries of EREs made it possible to develop rules that predict whether E R binds to a given natural ERE and also to predict the relative amount s of binding when comparing two EREs.