February 26, 2021

Epigenomics - Future Medicine

Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell.

Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair.

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Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.

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DNA methylation

The first epigenetic modification to be characterized in depth was DNA methylation. As its name implies, DNA methylation is the process by which a methyl group is added to DNA. The enzymes responsible for catalyzing this reaction are the DNA methyltransferases (DNMTs). While DNA methylation is stable and heritable, it can be reversed by an antagonistic group of enzymes known as DNA de-methylases. In eukaryotes, methylation is most commonly found on the carbon 5 position of cytosine residues (5mC) adjacent to guanine, termed CpG dinucleotides.

DNA methylation patterns vary greatly between species and even within the same organism. The usage of methylation among animals is quite different; with vertebrates exhibiting the highest levels of 5mC and invertebrates more moderate levels of 5mC. Some organisms like Caenorhabditis elegans have not been demonstrated to have 5mC nor a conventional DNA methyltransferase; this would suggest that other mechanisms other than DNA methylation are also involved.

Within an organism, DNA methylation levels can also vary throughout development and by region. For example, in mouse primordial germ cells, a genome wide de-methylation even occurs; by implantation stage, methylation levels return to their previous somatic values. When DNA methylation occurs at promoter regions, the sites of transcription initiation, it has the effect of repressing gene expression. This is in contrast to unmethylated promoter regions which are associated with actively expressed genes.