A mathematical approach to predict the affinity of estrogen receptors alpha and beta binding to DNA

Estrogen receptors alpha and beta (ER alpha and ER beta) bind to specific D NA sequences, estrogen response elements (EREs), usually located in the pro moters of estrogen-regulated genes. The consensus ERE contains two inverted repeats of the 5'-AGGTCA-3' half-site (1/2 ERE) separated by three base pa irs (bp). Many estrogen-responsive gene promoters contain one or more direc t repeats (DR) of 1/2 ERE. Here, we examined the affinity of ER alpha and E R beta binding and estradiol (E-2)-induced transactivation front select ERE s and DRs. The affinity of ER alpha and ER beta binding to imperfect EREs i n vitro can be predicted from equations using the number of 1/2 EREs and th e number of (AT) (GC) bp substitutions within the 15-bp candidate ERE Seque nce as independent variables. Transactivation by ER alpha and ER beta corre lates with the affinity of ER-ERE binding with the exception of ER alpha fr om two low-affinity EREs. The equations developed here can be used to scree n the promoters of estrogen-responsive genes for candidate ERE sequences. ( C) 2001 Elsevier Science Ireland Ltd. All rights reserved.