ESTROGEN RESPONSE ELEMENTS

Binding of an agonistic or antagonistic ligand to ER results in allosteric changes in the receptor leading to the dissociation of heat-shock proteins and the dimerization of ER. Estrogen receptors a and b can both homodimerize and, less frequently, heterodimerize. The ligand-receptor complex binds to chromatin-organized DNA sequences in the regulatory region of a target gene. ER binding causes a bend in the DNA toward a major groove and facilitates the interactions of key transcriptional components. Basal transcription factors, co-activators and repressors, as well as proteins that regulate chromatin remodeling signal for the activation or repression of target gene expression. The specific DNA sequences to which both ER-a and ER-b bind with high affintity are referred to as estrogen response elements (ERE). As Class I receptors, ER binds to palindromic repeats in a dimeric head-to-head arrangement. The minimal ERE consensus sequence is :

 

5’-GGTCAnnnTGACC-3’ (n=any nucleotide)

 

Non ERE-directed transcriptional activity has also been described. Evidence suggests that ligand bound receptor complexes may initiate transcription through interaction with other transcription factors, for example, ERa interaction with Sp1 or ERa and b interaction with AP-1 transcription factors c-fos and c-jun.

 

Reference: Klock G, Strahle U, Schutz G. Oestrogen and glucocorticoid responsive elements are closely related but distinct. Nature. 1987 Oct 22-28;329(6141):734-6.

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