In our present study, BIX diminished the interactions of EHMT2 with DNMT1 and the addition of 5-Aza-Cd synergistically reactivated Beclin-1 in breast cancer cells, which could be partially accounted for by the reversal of an ‘epigenetic double lock’ for gene silencing by both DNA and histone methylation. The gene discussed is BECN1; the disease is breast cancer.