Transcriptional repression by promoter DNA hypermethylation and histone modifications. In normal cells, the CpG islands of promoter regions are open chromatin and generally unmethylated. Gene transcription is activated by transcriptional factors with H3K27ac (left). In cancer cells, the CpG islands in the promoter regions are hypermethylated, constructing heterochromatin with H3K27me3 and H3K9me3, which suppresses gene transcription (right). Abbreviations: H3K27me3, trimethylation of lysine 27 on histone 3; H3K9me3, trimethylation of lysine 9 on histone 3; H3K27ac, acetylation of lysine 27 on histone 3.