Response element sequence modulates estrogen receptor α and β affinity and activity

The relationship between estrogen receptor (ER)-estrogen response element (ERE) binding affinity and estradiol (E₂)-induced transcription has not been systematically or quantitatively tested. We examined the influence of ERE palindrome length and the 3′ ERE flanking sequence on ERα and ERβ affinity binding in vitro and on the induction of reporter gene activity in transfected cells. The addition of one nucleotide in each arm of the 13 bp ERE palindrome, forming a 15 bp ERE palindrome, increased ERα and ERβ affinity and transcription. In contrast, the addition of an AT-rich flanking sequence from genes highly stimulated by E₂ had little effect on affinity or reporter gene activity. Notable differences between ERα and ERβ include: both K_d and transcriptional induction were generally higher for ERα than ERβ, better correlation between ERE palindrome length and transcriptional induction for ERα than ERβ, and a better correlation between (ER-ERE) K_d and transcriptional induction for ERα than for ERβ.