DNA methylation and regulation of gene expression: Guardian of our health

Abstract

One of the most critical epigenetic signatures present in the genome of higher eukaryotes is the methylation of DNA at the C-5 position of the cytosine ring. Based on the sites of DNA methylation in a locus, it can serve as a repressive or activation mark for gene expression. In a crosstalk with histone modifiers, DNA methylation can consequently either inhibit binding of the transcription machinery or generate a landscape conducive for transcription. During developmental phases, the DNA methylation pattern in the genome undergoes alterations as a result of regulated balance between de novo DNA methylation and demethylation. Resultantly, differentiated cells inherit a unique DNA methylation pattern that fine tunes tissue-specific gene expression. Although apparently a stable epigenetic mark, DNA methylation is actually labile and is a complex reflection of interaction between epigenome, genome and environmental factors prior to birth and during progression of life. Recent findings indicate that levels of DNA methylation in an individual is a dynamic outcome, strongly influenced by the dietary environment during germ cell formation, embryogenesis and post birth exposures. Loss of balances in DNA methylation during developmental stages may result in imprinting disorders, while at any later stage may lead to increased predisposition to various diseases and abnormalities. This review aims to provide an outline of how our epigenome is uniquely guided by our lifetime of experiences beginning in the womb and how understanding it better holds future possibilities of improvised clinical applications.

DNA methylation meta-analysis confirms the division of the genome into two functional groups

“…DNA methylation, which affects chromatin state and gene expression, is one of the most studied processes of genomic regulation today [1, 2]. The specifics of the regulatory function of methylation continue to be studied, but there is no doubt that this process is related to ontogenetic development and aging [3,4].…”

A Deep Learning–Based Framework for Supporting Clinical Diagnosis of Glioblastoma Subtypes

“…The recent reports show that the hypermethylation/hypomethylation level in the promoter region (e.g., defined as TSS1500 upstream to TSS200 downstream of TSS, 5′UTR, and first exon; TSS denotes transcription start site) and gene body determine the gene expression level ( Sandoval et al, 2011 ; Yang et al, 2014 ). Therefore, we screened the promoter and gene body methylation data to perform classification because the alteration of methylation levels in these regions can influence the gene expression level and subsequently influence the biological processes ( Dhar et al, 2021 ). The CpG sites, which include all promoter regions and the gene body, were screened for feature selection.…”

Impact of epigenetics on human health and possible tool for remediation

“…A fine balance maintains the normal profile of the cell and an imbalance can be associated with development of diseased states including cancer, neuronal disorder, impaired DNA repair, exposure associated disorders [6,27,42,51]. In the present issue, Dhar et al [12] and Banerjee et al [2] outlines some of the major aspects of DNA methylation and how it affects gene expression and development of neuronal disorder like autism. In both the articles, issues relating to genomic imprinting have been discussed along with how understanding epigenetic alterations can help in countering these disorders in humans, clinically.…”

“…With age, the reproductive phase peaks and gradually fades out. In this edition, Chandra et al presents elaborately on the physiological importance of GnRH genes, age associated changes in their expression and how epigenetic guardians [12] like DNA methyl transferases (DNMTs), ten-eleven translocases (TETs), play crucial role in fine tuning the expression of these genes [8].…”