Activation Function 2 (AF-2) within estrogen receptors (ERα and ERβ) serves as the binding site for cofactors, facilitating transcription. The recruitment of these cofactors to estrogen receptors depends on both the type of ligand bound and the sequence of the estrogen response element (ERE).
When the receptors bind to the 17β-estradiol (E2) ligand, the specific ERE sequence predominantly guides the recruitment of AF-2-dependent cofactors. In this case, the ERE sequence dictates the selection of cofactors.
Conversely, when anti-estrogens occupy the estrogen receptors, the influence of the ERE sequence on AF-2-dependent cofactor recruitment diminishes, and the ligand itself becomes the primary determinant for cofactor recruitment.
