Abstract

Monitoring Biological Methylation and its Role in Human Health

Said A Goueli, Clinical Professor and Senior Research Fellow, Promega Corporation

Epigenetics is defined as the heritable traits that are independent of DNA sequence but involves chemical changes within chromatin. These chemical changes encompass posttranslational modifications of histone proteins, DNA methylation and oxidative events, and the more recently methylation and demethylation of mRNA and LncRNA as well. The modifications of histones, DNA and RNA modulate chromatin structure and result in altered gene expression. The epigenetic signature is written, erased, and read by specific enzymes and proteins that control the epigenome and result in altered cellular phenotype. These include methyltransferases and demethyltransferass, acetyltransferases and deacetylases. Although histone acetylation usually activates transcription, methylation of histones results in either activation or repression of transcription depending on the enzymes involved and the site and level of methylation of chromatin proteins. In addition to the role of m6A in splicing, translation, and stability of mRNA, it also controls processing and abundance of miRNAs. Thus, understanding how RNA methylation controls these processes is of paramount importance. Aberrant methylation of chromatin proteins, DNA, and RNA are intimately implicated in multiple and diverse pathologies which includes cancer, inflammatory responses, and metabolic disorders. Furthermore, methylation of small molecules such as L-DOPA is well recognized to be a validated target for the development of drugs for the treatment of Parkinson disease. This presentation will address the role of methylation in the development of normal and abnormal cellular behavior and we will present the latest approach to monitor the activity of these methylating enzymes in a universal manner, thus facilitating the search for, and discovery of novel therapeutics.