[Acquired disorders and epigenetics].
Epigenetic modifications, involving DNA methylation and histone modifications, are maintained upon somatic cell replication, and are fundamental mechanisms for cellular memory. DNA methylation of promoter CpG islands of tumor-suppressor genes can silence their downstream genes, and can be causally involved in cancer development and progression. Since this effect is the same with that of inactivating mutations, the natures of DNA methylation were once considered to be similar to mutations. However, recently, it was revealed that a large number of epigenetic alterations are present in a single cancer cell, that a large number of cells have an epigenetic alteration of a specific gene in non-cancerous, thus polyclonal, tissues, that gene specificity in methylation induction is present according to tissue types and inducers, and that chronic inflammation is deeply involved in methylation induction. These facts suggest that epigenetic alterations of key genes involved in acquired chronic disorders can be present in a significant fraction of cells in a tissue, and thus can impair the function of the tissue. Associations between epigenetic alterations and behavior, memory, mental disorders, neurological disorders, metabolic disorders, allergy, autoimmune disorders, and other disorders have been reported. Further research in the field is necessary to clarify the causal roles of these epigenetic alterations in disease development, and to apply the findings to new strategies of disease prevention, diagnosis, and treatment.
Ushijima
Toshikazu
T
Carcinogenesis Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D014158:Transcription, Genetic
D006657:Histones