ESR1 and breast cancer: Critical for transcription regulation by ER is the ordered recruitment of a multitude of transcriptional co-regulator complexes with enzymatic activities for histone modification and chromatin remodeling (Métivier et al., 2006), which promote short- and long-range protein-DNA and protein-protein interactions between enhancer regions and gene promoters, to facilitate expression of ER target genes that drive breast cancer cell proliferation.