Mechanistically, quantitative histone methylation proteomics and cleavage under targets and tagmentation (CUT&Tag) technology jointly revealed that Cd‐induced MTA depletion specifically decreased the activity of the DOT1L methyltransferase and increased H3K79me1 levels in the P21‐activated kinase 2 (PAK2) promoter region, facilitating the expression of PAK2, which contributes to the autophagic flux blockage that is required for BC progression. The gene discussed is PAK2; the disease is breast cancer.