Histone proteins constitute the core component of the
nucleosome, the basic unit of
chromatin. Chemical modifications of
histone proteins affect their interaction with genomic
DNA, the accessibility of recognized
proteins, and the recruitment of enzymatic complexes to activate or diminish specific transcriptional programs to modulate cellular response to extracellular stimuli or insults. Methylation of
histone proteins was demonstrated 50 years ago; however, the biological significance of each methylated residue and the integration between these
histone markers are still under intensive investigation. Methylation of
histone H3 on
lysine 27 (H3K27) is frequently found in the
heterochromatin and conceives a repressive marker that is linked with gene silencing. The identification of
enzymes that add or erase the methyl group of H3K27 provides novel insights as to how this
histone marker is dynamically controlled under different circumstances. Here we summarize the
methyltransferases and demethylases involved in the methylation of H3K27 and show the new evidence by which the H3K27 methylation can be established via an alternative mechanism. Finally, the progress of drug development targeting H3K27 methylation-modifying
enzymes and their potential application in
cancer therapy are discussed.