It has been previously reported that the pioneers TFs FOXA1 and GATA3 mediated ESR1 binding by shaping enhancer accessibility (Theodorou et al., 2013); FOXA1 collaborates with GRHL2 and MLL3 to establish a targetable collateral pathway in endocrine therapy-resistant breast cancer (Werner et al., 2013; Cocce et al., 2019). The gene discussed is KMT2C; the disease is breast cancer.