Working model of the Notch–ERα crosstalk. The Notch transcriptional complex (NTC) including Notch-1, CSL, MAML1 (MAM) and other coactivators (not shown for clarity) binds to Notch-CSL-responsive elements (NCRE). IKKα is recruited to the NTC in a Notch-dependent manner, although it is still unclear whether the interaction with Notch is direct and is necessary for formation of the supramolecular complex. ERα is recruited to the nucleus in a Notch-1-dependent manner, binds to its responsive element (ERE) or possibly through other transcription factors or pioneer factors, and is necessary for NTC recruitment to ERα-responsive genes. In the absence of E2, MAML1 recruits p300 to the complex, taking over the functions normally carried out by p160 ERα coactivators. The formation of a supramolecular complex between the NTC and the ERα transcriptional complex contributes to activate transcription of a subset of ERα-responsive genes in the absence of E2, and for some genes also in its presence. The pol-II complex is depicted at the TATA box with its most important components. The angled green arrow indicates transcriptional start. ER, estrogen receptor; ERα, estrogen receptor-α.