Macaluso and coworkers [46] demonstrated that the transcriptional silencing of ER-α is mediated by two multiprotein repression complexes (1) pRb2/p130-E2F4/5-HDAC1-histone methyl transferase (SUV39H1)-p300 and (2) pRb2/p130-E2F4/5-HDAC1-DNMT1-SUV-39H1 that are recruited to the ER-α promoter of breast cancer cells. The gene discussed is E2F4; the disease is breast cancer.