ESR1 and breast carcinoma: The identification of ESR1-responsive enhanceosome hypermethylation is both novel and considerably pertinent in the context of endocrine resistance, since genome-wide positional analyses defining the set of cis-regulatory elements that recruit ESR1 in breast cancer cells have revealed its predominant recruitment to enhancers as opposed to promoter regions3, 27, 28, 29, 30.