Alterations in histone H4 lysine 20 methylation: implications for cancer detection and prevention.

SIGNIFICANCE: Cancer development and progression are associated with numerous genetic, epigenetic, and metabolic changes. RECENT ADVANCES: A number of epigenetic aberrations have been characterized in cancer, including DNA methylation and various histone modification changes. One of the most unique and enigmatic epigenetic marks that is noticeably altered in several major human cancers is methylation of histone H4 lysine 20; however, there is insufficient knowledge of the underlying molecular mechanisms associated with this abberation. CRITICAL ISSUES: This review presents current evidence of the role of histone H4 lysine 20 methylation in normal and cancer cells and during tumorigenesis induced by genotoxic and nongenotoxic carcinogens. Additionally, it describes molecular mechanisms that may cause this alteration and highlights the significance of this epigenetic mark as an early indicator of carcinogenesis. FUTURE DIRECTIONS: Accumulating evidence suggests that dietary components may be significant regulators of the cellular epigenome, including histone methylation, by providing and maintaining the adequate levels of S-adenosyl-L-methionine, flavin adenine dinucleotide, α-ketoglutarate, and iron. Future research should elucidate the potential for modifying cellular metabolism through dietary intervention for timely regulation of the epigenome as means for the prevention of cancer development.