Der Über-Code der DNA: Epigenetische Mechanismen und deren Bedeutung für die Entstehung von Krankheiten

Abstract

The deciphering of epigenetic changes is of increasing importance for our current understanding of phenotypes and disease. The term epigenetics describes meiotically and/or mitotically inheritable changes of gene expression, which are not encoded in the DNA sequence itself. Epigenetic mechanisms include modification of DNA, histones, and chromatin proteins, the expression of non-coding RNAs as well as nuclear positioning of genes. A number of locusspecific and genome-wide methods exists allowing characterization of epigenetic patterns and changes. These range from methylation-specific PCR to whole-genome bisulfite sequencing as well as from chromatin-immunoprecipitation to conformation analyses using HiC. Alterations of epigenetic modifications and mechanisms are associated with rare monogenic disorders and imprinting defects and also with common diseases. The latter might already be determined at least, in part, through prenatal epigenetic programming. Particularly in cancer cells, a huge number of epigenetic alterations can be observed. These include strong changes in DNA methylation as well as mutation of genes involved in epigenetic mechanisms. As epigenetic changes are reversible, various drugs have been developed targeting epigenetic modifications, like HDAC inhibitors or demethylating drugs. This article reviews the most common epigenetic mechanisms as well as epigenetic changes and their detection in health and disease.