Gene expression profiling and approaches for genome-wide identification of ER binding regions have allowed the identification of direct ER targets in breast cancer cells and highlight the importance of pioneer factors, particularly FOXA1 and GATA3 in directing ER by promoting chromatin accessibility and long-range chromatin interactions (Magnani et al., 2011; Ross-Innes et al., 2012). The gene discussed is ESR1; the disease is breast cancer.