Fig. 4: Cancer epigenetics.
From: Epigenetic regulators in cancer therapy and progression
DNA methylation, histone modifications, and chromatin remodeling are the three main epigenetic changes that drive the progression of cancer. DNA methylation changes include promoter hypermethylation, which suppresses tumor suppressor genes because of increased DNMT activity and decreased TET protein activity; on the other hand, genome-wide hypomethylation, which is frequently caused by decreased DNMT activity, causes genomic instability and oncogene activation; histone modifications include mutations in Histone Methyltransferases (HMTs), Histone Demethylases (HDMs), and histone variants like H3.3, which result in abnormal methylation patterns; and reduced histone acetylation, which further suppresses normal gene expression and contributes to cancer. Defects in chromatin remodeling, including loss-of-function mutations in SWI/SNF complexes, produce condensed chromatin structures that impair regular gene regulation and increase the likelihood of tumor development. These linked alterations result in aberrant chromatin architecture and dysregulated gene expression, which are characteristics of cancer194.
