Epigenetics
Epigenetics refers to the study of heritable changes in gene expression that occur without any alteration in the underlying DNA sequence. These changes can be influenced by various environmental factors, such as diet, stress and exposure to toxins. Epigenetic modifications can occur at different levels, including DNA methylation, histone modification and non-coding RNA (ncRNA) expression, and can result in altered gene expression patterns that can persist across generations. Epigenetic modifications can play a critical role in development, ageing and disease susceptibility, and understanding the underlying mechanisms of epigenetic regulation is an active area of research in biology and medicine.
An important function of epigenetic processes is purely data management; that is, ensuring the genetic information is suitably packaged in the nucleus of a cell. The human genome comprises approx. 3 billion bps organised into 23 chromosomes. Each diploid cell has 46 chromosomes and therefore contains 6 billion bps of DNA, each base measures 0.34 nm, therefore in every nucleus of every diploid cell there must be 2 m of condensed DNA. The average person has approx. 70 trillion cells. Histones have an integral role in organising long strands of DNA as chromatin. Histone proteins H1, H2A, H2B, H3 and H4 are involved in compacting the DNA; 147 bps DNA is wrapped around dimers of histones H2A, H2B, H3 and H4 making up the nucleosome core.
The epigenome comprises a range of modifications to DNA, RNA and proteins (histones). It is controlled structurally and functionally by specific enzymes responsible for catalysing the reactions to lay down these epigenomic marks, and another set of enzymes responsible for removing both active and repressive marks to enable the epigenome to have plasticity and reversibility. The epigenomic marks are important in modulating gene expression; they are interpreted by other proteins and provide instructions, as to the activity of the gene or genes in the locality of the mark (see accompanying table).
Epigenetics focuses on heritable and potentially reversible changes to gene expression, which are not related to changes in the genomic DNA sequence. Mechanisms that regulate the transcription or gene expression levels that are cell- type or tissue-specific without altering the DNA. These mechanisms are biochemical modifications including the addition of a methyl group to cytosines as well as the post-translational modifications of histones. These mechanisms have a key role in cellular development, particularly in processes such as embryogenesis, cell differentiation, X inactivation and genomic imprinting.