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.
Date:
2018-01
Relation:
Cellular and Molecular Life Sciences. 2018 Jan;75(2):209-223.
