Mechanisms of estrogen receptor-mediated response

ERs within the nucleus of estrogen-responsive cells receive signals from extracellular estrogen (E2), which can pass through cell and nuclear membranes due to its lipophilic character. GFs, such as IGF-1 or EGF, bind and activate membrane receptors (GF receptor), which triggers a cascade of intracellular phosphorylation mediated signaling that activates the ER. Pioneer factors, such as FoxA1, facilitate ER access to ERE motifs in chromatin (steps 1 and 2). Estrogen- or GF-activated ER then recruits co-activators and chromatin remodelers (step 2). The activities of the chromatin remodelers allow RNA polymerase II (RNA Pol II) to access the TSS (steps 3 and 4), resulting in the initiation of RNA transcription.