In this study, we report for the first time that (i) BRCA1-mutated breast cancer displayed a hypermethylated E2F1 motif and promoter region; (ii) the hypermethylated E2F1 motif was negatively correlated with DNMT1 mRNA levels; and (iii) E2F1 is a key transcriptional regulator of DNMT1. Here, E2F1 is linked to breast cancer.