title: A mathematical approach to predict the affinity of estrogen receptors alpha and beta binding to DNA.
abstract: Estrogen receptors alpha and beta (ERalpha and ERbeta) bind to specific DNA sequences, estrogen response elements (EREs), usually located in the promoters 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 pairs (bp). Many estrogen-responsive gene promoters contain one or more direct repeats (DR) of 1/2 ERE. Here, we examined the affinity of ERalpha and ERbeta binding and estradiol (E(2))-induced transactivation from select EREs and DRs. The affinity of ERalpha and ERbeta binding to imperfect EREs in vitro can be predicted from equations using the number of 1/2 EREs and the number of (AT)-(GC) bp substitutions within the 15-bp candidate ERE sequence as independent variables. Transactivation by ERalpha and ERbeta correlates with the affinity of ER-ERE binding with the exception of ERalpha from two low-affinity EREs. The equations developed here can be used to screen the promoters of estrogen-responsive genes for candidate ERE sequences.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: V V
authors.initials: VV
authors.lastname: Tyulmenkov
authors.forename: C M
authors.initials: CM
authors.lastname: Klinge
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D017930:Genes, Reporter; D006801:Humans; D008962:Models, Theoretical; D011485:Protein Binding; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D020218:Response Elements; D020080:Tandem Repeat Sequences; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D004247:DNA