Epigenetics: overview

Epigenetics is both heritable and a reversible interaction on the DNA, resulting in a change in expression or phenotype without altering the DNA sequence. Epigenetic effectors include the modification of DNA by methylation, the configuration and modification of nucleosomal histone proteins and the involvement of antisense RNA molecules. Epigenetics, in association with the transcriptional apparatus, regulates transcriptional profiles which dictate changes in cellular phenotype, controlling cell differentiation, division and death.

During mammalian development, a specific mechanism of epigenetic regulation is in place that acts on a small number of genes controlling some aspects of fetal growth and development and postnatal behaviour. This mechanism, known to involve approximately 100 genes in the mouse genome and 50 genes in the human genome, is characterised by parent-of-origin-specific monoallelic expression, and is known as genomic imprinting (see www.otago.ac.nz/IGC).

Genomic imprinting

Genomic imprinting was discovered in 1984 by pronuclear transfer experiments. Bipaternal and bimaternal embryos were created in parallel to reveal opposite lethal phenotypes. The genomes inherited from the mother and the father during sexual reproduction were found to be asymmetrical, and each indispensible in normal development (Figure 5.1).

Naturally occurring examples of these phenotypes can be found in humans and they are also incompatible with life. Ovarian teratomas are equivalent to gynogenotes and are characterised by varying stages of developing embryonic tissues, which are grossly disorganised. Hydatidiform moles are equivalent to androgenotes and take the form of overgrown and cystic trophoblast tissue, which can become highly invasive.