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Environmental Health Sciences

Introduction to Epigenetics

Epigenetic regulation is the heritable change in gene expression that occurs in the absence of alterations in DNA sequences. The term "epigenetics" means "outside conventional genetics." A variety of molecular mechanisms are involved in epigenetic regulation of gene expression and chromosomal stability, including histone modifications, non-coding RNA and DNA methylation. In the past, it has been thought that DNA was the only source of what determined the susceptibility of disease but recently it has been shown that epigenetic changes can play an equally important role. As of late, scientists are looking into the role the environment plays on epigenetic modifications to see if there is a change in gene expression and phenotype.


DNA methylation, the best-studied epigenetic mechanism, is a process that suppresses gene expression via the covalent addition of a methyl group from S-adenosyl-L-methionine (SAM) to a 5-carbon of cytosine residue in a CpG site (where a cytosine lies next to guanine), to form 5-methylcytosine (5-mC). DNA methylation is established by three different DNA methyltransferases (DNMTs): i) the de novo activity by DNMT3A and 3B and ii) the maintenance activity by DNMT1. Existence of 5-mC prevents binding of transcription activators at their recognized region, leading to decreased gene transcription. In contrast, DNA demethylation, the process of removal of 5-mC, is proposed to be regulated through base-repair excision (BER), but the processes by how demethylation occurs were not well established until recently. Oxidation of 5-mC to 5-hydroxymethylcytosine (5-hmC) by 5-mC dioxygenase, TETs, has been demonstrated as a novel mechanism of epigenetic regulation that may contribute to remove DNA methylation.