Epigenetics is the study of heritable changes in gene expression or cellular phenotype that is caused by mechanisms that do not involve changes in DNA sequence. In practice, epigenetics is the study of gene expression or phenotype changes. The Greek word ‘epi’ means over, above or outer and the word genetics means study of genes. The term ‘epigenome’ refers to the overall epigenetic state of a cell genome. ‘Epigenetic inheritance’ describes the ability of different states of the DNA, which may have different phenotypic consequences to be inherited without any change in the sequence of the DNA. This means that two individuals even if they have same DNA sequence may show different phenotypes. Some of the epigenetic effects include:
- A covalent modification of DNA (methylation of DNA bases).
- A proteinaceous structure that assembles on the DNA.
- A protein aggregate that controls the conformation of new subunit as they are synthesized.
These changes may remain through cell division for the remainder of the cell’s life and may also last for multiple generations. However, there is no change in the underlying DNA sequence of the organism instead, non-genetic factors cause the organism’s genes to behave (or ‘express themselves’) differently.
In case of DNA methylations, a DNA sequence methylated in its control region may fail to be transcribed, while the unmethylated sequence will be expressed. Certain proteins that assemble on the DNA usually have a repressive effect by forming heterochromatin regions that prevent the expression of genes within them. Usually the tails of histone H3 and H4 are not acetylated in constitutive heterochromatin. If the centromeric heterochromatin is acetylated, silenced genes may become active. The effect may be continued through mitosis and meiosis. The molecular basis of epigenetics is a complex phenomenon and involves changes in the switching ‘on’ and ‘off’ of certain genes.
Epigenetics is widely used in diagnostics and research. Epigenetics finds applications in a wide range of molecular biologic techniques including: methylation-specific PCR (MSP), popular chromatin immunoprecipitation, bisulphite sequencing, FISH, methylation-sensitive restriction enzymes and DNA adenine methyltransferase identification. The use of bioinformatic methods is playing an increasing role in computational epigenetics.
The important role of epigenetic defects analysis in cancer opens up new and exciting opportunities for improved diagnosis and therapy.