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Epigenetic Mechanisms

The field of Epigenetics encompasses various mechanisms, including DNA methylation, histone modification, and microRNA. DNA methylation is a covalent, heritable modification in somatic cells after cell division. 5-methyl-cytosine (5MeC) represents 2-5% of all cytosines in the mammalian genome and is mainly present in CpG dinucleotides. DNA methylation is involved in the regulation of numerous cellular processes, including chromatin structure and remodeling, X chromosome inactivation, genomic imprinting, chromosome stability, and gene transcription. Generally, hypermethylation of gene promoters is associated with decreased gene expression.

Histones are globular proteins that undergo post-translational modifications altering their interaction with DNA and other nuclear proteins. Histones H3 and H4 have long tails protruding from the nucleosome and which can be covalently modified by acetylation, methylation, ubiquitination, phosphorylation, sumoylation, citrullination, and ADP-ribosylation, thus influencing chromatin structure and gene expression.

MicroRNAs (miRNA) are single-stranded RNA molecules, 21-23 nucleotides long, transcribed from DNA but not translated into proteins (non-coding RNA); mature miRNAs are partially complementary to one or more messenger RNA (mRNA) molecules. The main function of miRNAs is to negatively regulate gene expression by interfering with mRNA functions. Some environmental factors have been linked to aberrations in epigenetic pathways in both experimental and epidemiological studies. Moreover, epigenetic mechanisms may mediate responses to certain chemicals and convey specific toxicity mechanisms. While the mechanisms of action of some of these agents are well known, for others, the mode of action remains to be fully elucidated. Since these epigenetic changes are of small magnitude, potentially cumulative, and may develop over time, establishing cause-effect relationships between environmental factors, epigenetic changes, and diseases could be challenging.

References

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