Epigenetics refers to reversible and heritable changes in gene expression that occur without altering the underlying DNA sequence.
Explanation
Epigenetic mechanisms regulate how and when genes are expressed in different cell types and developmental stages. DNA methylation involves addition of a methyl group to cytosine bases, particularly within CpG dinucleotides, leading to transcriptional repression when present in gene promoters. Histone modifications such as acetylation, methylation, phosphorylation and ubiquitination alter chromatin structure and accessibility to transcription factors. Chromatin remodelling complexes reposition nucleosomes to expose or occlude regulatory regions. Non‑coding RNAs, including microRNAs and long non‑coding RNAs, can recruit chromatin modifiers or degrade messenger RNA. These mechanisms interact to create an epigenetic landscape that is dynamic yet faithfully propagated during cell division. Environmental factors such as diet, stress, toxins and aging can influence epigenetic marks, and some modifications can be transmitted to offspring through gametes. Epigenetic dysregulation contributes to cancers, neurological disorders and metabolic diseases by aberrantly activating oncogenes or silencing tumour suppressor genes. Unlike DNA sequence mutations, epigenetic changes are potentially reversible, making them attractive targets for therapy.
Notable examples
During mammalian development one X chromosome in female cells is inactivated through DNA methylation and histone modifications, ensuring dosage compensation. Genomic imprinting results from parent‑specific methylation patterns that silence one allele of certain genes, as in the IGF2/H19 locus. Silencing of tumour suppressor genes such as CDKN2A by promoter methylation is common in cancers. Histone acetylation in hippocampal neurons facilitates transcription of genes involved in learning and memory. The Dutch Hunger Winter provided evidence that maternal famine can induce epigenetic changes in offspring affecting metabolism. In plants, paramutation at the b1 locus of maize involves trans‑generational alteration of gene expression without DNA sequence change. Drugs such as azacitidine, a DNA methyltransferase inhibitor, and histone deacetylase inhibitors like vorinostat are used clinically to reverse aberrant epigenetic repression.
Epigenetics bridges the gap between genotype and phenotype by explaining how the same genome can produce diverse cell types and respond to environmental cues. Understanding epigenetic regulation offers insights into development, disease and the potential for therapeutics that modify gene expression without changing DNA sequences.
Related Terms: DNA methylation, Histone modification, Chromatin, Non‑coding RNA, Genomic imprinting