Melita Vidakovic, PhD, Principal Research Fellow
Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, University of Belgrade
CSI: CELL Expert lecture
Relationship between genome and epigenome: challenges and requirements for future research in diabetes attenuation
Epigenetics studies genetic factors and mechanisms that regulate the expression of the genetic code without altering the DNA sequence. Epigenetic processes regulate the expression of genes by chemical modifications of DNA and chromatin structural proteins by DNA methylation and various forms of post-translational modifications of histones, respectively, and through the actions of small noncoding RNA molecules.
The main objective of epigenetic research groups is to define the mechanisms of epigenetics modifications that lie at the basis of an epigenetic process. There are a several basic priorities for future research in epigenetics: the establishment of links between genetic, epigenetic and environmental factors over the life cycle and across generations, defining their roles in health and disease, and determining the significance for the development of predisposition and progression of specific diseases.
A large number of scientific publications suggest that disturbances in mechanisms which regulate epigenetic processes underlie several complex pathologies, including diabetes mellitus as a complex metabolic disorder. For diabetes, the therapy challenges lie in identifying the most appropriate key molecule that should be targeted on a relevant gene. This lecture, summarizes the current view on (i) genome editing using the CRISPR-Cas 9 epigenetic tool and (ii) on the interplay between Ten-eleven translocation (TET) and poly(ADP-ribose) polymerase (PARPs) family of enzymes in regulating DNA methylation and how this triangle can influence diabetes attenuation. This complicated jigsaw puzzle is only now emerging as an important research topic and in future we should expect to see more advances in elucidating the role this interplay has in diabetes and other pathologies. Moreover, we will discuss the possibility for positioning preferred PARP-1 inhibitors in the range of potentially new “EPI-drugs” for diabetes prevention/attenuation. Understanding the epigenetic machinery and the differential roles of its components is essential for developing more targeted epigenetic therapy for the common non-cancerous diseases.