Estrogen receptor action through target genes with classical and alternative response elements (original) (raw)

2000, Pure and Applied Chemistry

The estrogen receptors alpha and beta (ERα and ERβ) mediate the changes in gene expression from physiological and environmental estrogens. Early studies identified classical estrogen response elements (EREs) in the promoter region of target genes whose expression is regulated by estrogen and to which the ERs bind via their DNA-binding domain (DBD). EREs in the pituitary prolactin promoter, for example, mediate an activation by both ERα and ERβ albeit with different affinities for different ligands. Full activation in most cell types requires the integrity of the activation function 2 (AF-2) in the receptors ligand binding domain (LBD), which is engaged by estrogens and disengaged by tamoxifen, raloxifene, and other antiestrogens. However, in some cells and ERE contexts, the AF-1 in the ERα amino terminal domain (NTD) is sufficient.We now know that ERs also regulate expression of target genes that do not have EREs, but instead have various kinds of alternative response elements that ...