ESR1 and breast cancer: Since the vast majority of ESR1-enhancer-binding sites identified as hypermethylated in the endocrine-resistant cell lines compared with the parent MCF7 cells were intragenic (that is, 617 out of 856, 72% with at least partial overlap; Supplementary Data 1), we next sought to determine if the DNA methylation of these regions correlated with the expression of the genes in which they were located (or closest TSS if intergenic) in human breast cancer.