Thursday, March 10, 2011

testing a central tenet of epigenetic regulation

The Scientist | A fundamental problem in biology concerns how the genomic information present in fertilized eggs can give rise to the full spectrum of stably differentiated cell types required to form vertebrates and invertebrates. In the 1930s, C.H. Waddington’s largely observational mammalian embryology studies, which defined this problem, were central to establishing the field of epigenetics. It is now well known that there are master regulatory genes that must be kept on to specify a given cell lineage and off in the many other cell lineages that make up the body.

The problem of keeping these genes in the off state when required has received considerable attention, in large part due to the landmark genetic studies initiated by Pam and Ed Lewis in the 1940s that identified a set of genes required for this repression. This family of genes is called the Polycomb Group (PcG) because the visual phenotype of a heterozygous null allele in these genes is duplication on the second and third legs of the sex combs that wild-type male Drosophila flies have on their front legs. It turns out that PcG proteins repress key developmental master regulatory genes in organisms from plants to humans. The PcG is responsible for a diversity of important biological events, from why plants flower only in the spring (and not in a December warm spell) to how mammals form the correct body tissues in the correct locations.