Gavin Kelsey

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Imprinted genes: epigenetic regulation of the genome

The activity of our genes is determined by more than just DNA sequence, as exemplified by epigenetic phenomena such as genomic imprinting.  Imprinting results in the deliberate silencing of one copy (allele) of specific genes, according to whether the allele comes from the father or mother.  Imprinted expression is the product of multiple developmental decisions: differences in epigenetic marking of sequences in the male and female gametes (the egg and sperm); persistence of these marks in somatic tissues of the developing embryo and into adult life; and translation of marks into different states of activity of the two alleles.  This memory of parental origin has profound implications for normal growth and development and metabolic health throughout life.  Correct epigenetic programming in the egg and sperm may also be essential for normal fertility.

A key question is what dictates which of our 30,000 genes is imprinted.  Recent work in our group has identified a novel role for transcription in helping to establish the epigenetic marks that define imprinted genes in germ cells. We are now applying genome-wide analysis to ascertain the extent of DNA methylation in gametes, its fate in early embryos, its impact on gene activity in somatic tissues and whether lifetime exposures alter methylation marks. (More...)

Figure: (Click to enlarge)
The DNA methylation life cycle