Basics of Epigenetics and Role of Epigenetics in Diabetic Complications

Abstract

The term "Epigenetics" includes mechanisms by which genetic expression is altered without a change in the underlying DNA sequence. The changes caused by epigenetic mechanisms are inheritable and are one way in direction (irreversible) and also explains why there is differences in genetic expressions of monozygotic twins. The epigenetic mechanisms alter the genetic expressions through DNA methylation, posttranslational modifications (PTMs) of histone, and noncoding RNAs. DNA methylation and histone PTMs cause relaxation or condensation of chromatin units. The epigenetic actions of noncoding RNAs such as microRNAs, small nucleolar RNAs, small interfering RNAs, and long noncoding RNAs act by modifying transcription factors or by degrading target messenger RNAs and their translation factors. Various pathologies and environmental factors cause changes in the cellular epigenetic mechanisms and the epigenetic alterations occurring in diabetes mellitus (DM) are reviewed. DM causes hemodynamic changes and metabolic changes like hyperglycemia and dyslipidemia. These changes induce oxidative stress and activate intracellular signaling and kinases in the target cells. Epigenetic alterations cause chromatin remodeling and altered gene expression leading to inflammation, proliferation, atrophy, hypertrophy, etc.; thereby, diabetic complications such as neuropathy, nephropathy, vasculitis result in the corresponding target organ. When these epigenetic alterations persist for a longer period without intervention, the target cells attain "metabolic memory" meaning that these epigenetic mutations cannot be reversed even after attaining normal blood glucose levels. Thus, epigenetics, an insightful and efficient tool in genomic research, has started crawling into the research arena and needs to reach leaps and bounds for the better understanding of health and diseases.

Keywords: DNA methylation; Diabetes mellitus; epigenetics; histone modification; long noncoding RNAs; microRNAs; noncoding RNAs; small interfering RNAs; small nucleolar RNAs.

Figure 1

Arrangement of DNA, chromatin, histones within a single chromosome[14]

Figure 2

Transcription and translation[6]

Figure 3

DNA methylation and posttranslational modifications in histone

Figure 4

Noncoding RNAs– classification and mechanism of action

Figure 5

Mechanism of action of small interfering RNAs[7]

Figure 6

Role of epigenetics in pathophysiology of diabetic complications[8]