REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Genetic mutations or regulatory failures underlie cellular malfunction in many diseases, including colorectal cancer and inflammatory bowel diseases. However, mutational defects alone fail to explain the complexity of such disorders. Epigenetic regulation-control of gene action through chemical and structural changes of chromatin-provides a platform to integrate multiple extracellular inputs and prepares the cellular genome for appropriate gene expression responses. Coregulation by polycomb repressive complex 2-mediated trimethylation of lysine 27 on histone 3 and DNA methylation has emerged as one of the most influential epigenetic controls in colorectal cancer and many other diseases, but molecular details remain inadequate. Here we review the molecular interplay of these epigenetic features in relation to gastrointestinal development, homeostasis, and disease biology. We discuss other epigenetic mechanisms pertinent to the balance of trimethylation of lysine 27 on histone 3 and DNA methylation and their actions in gastrointestinal cancers. We also review the current molecular understanding of chromatin control in the pathogenesis of inflammatory bowel diseases.

Automated summary

Mutational defects and epigenetic regulation play crucial roles in diseases like colorectal cancer and inflammatory bowel diseases. The interplay of epigenetic features, such as polycomb repressive complex 2-mediated trimethylation of lysine 27 on histone 3 and DNA methylation, are important in these diseases, but molecular details are still lacking. This review also discusses other epigenetic mechanisms relevant to gastrointestinal cancers and the current understanding of chromatin control in the pathogenesis of inflammatory bowel diseases.