Genetics, Epigenetic Mechanism

Epigenetics is the study of heritable and stable changes in gene expression that occur through alterations in the chromosome rather than in the DNA sequence. Despite not directly altering the DNA sequence, epigenetic mechanisms can regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure in which DNA is packaged.Briefly, negatively charged DNA is packaged around a positively charged histone protein octamer, which contains 2 copies of histone proteins H2A, H2B, H3, and H4. This nucleoprotein complex is a nucleosome, the basic unit of chromatin. The nucleosomes of a continuous DNA polymer are connected by linker DNA and the complex is stabilized by histone protein H1. The aggregation of chromatin results in the formation of a chromosome. The chromatin of a chromosome exists as either loose, transcriptionally active euchromatin or dense, transcriptionally inactive heterochromatin. Chemical alterations to histone proteins can induce the formation of either the open euchromatin state, which facilitates gene expression by allowing transcription factors and enzymes to interact with the DNA, or the closed heterochromatin state, which suppresses gene expression by preventing initiation of transcription.In addition to histone changes, DNA methylation is an epigenetic mechanism associated with gene silencing when the methylation occurs in CpG islands of promoter sequences. Further, non-coding RNA sequences have shown to play a key role in the regulation of gene expression. These epigenetic modifications can be induced by several factors including age, diet, smoking, stress, and disease state. Epigenetic modifications are reversible, but they rarely remain through generations in humans despite persisting through multiple cycles of cell replication.