Figure 4.

 A schematic representation of the proposed mechanism underlying histone modifications in the NY‐ESO‐1 promoter. (a) Methylation of lysine 9, moderate methylation of lysine 4, and hypermethylation of the CpG islands caused the formation of a folded chromatin structure, leading to NY‐ESO‐1 gene silencing. (b) 5‐aza‐2′‐deoxycytidine (DAC) dramatically decreases lysine 9 methylation, demethylates the CpG sites, and unfolds the chromatin, thus reactivating gene expression. (c) VPA increases lysine 9 acetylation but has no effect on the methylation of lysine 9 or lysine 4 and does not reverse transcriptional silencing. (d) The combination of DAC and VPA decreases lysine 9 methylation and increases lysine 9 acetylation, but does not affect lysine 4 methylation. This combination unfolds the chromatin to a considerable extent and reactivates gene expression with high efficiency.