A specific cell in the body needs to know what function it has and maintain this function for the entire life of the individual. This kind of "cell memory" is maintained by silencing proteins.
Mutations early in life in genes coding for such proteins might result in serious deformities, so that one body part is exchanged for another. If this happens later in life, the cell can lose its "memory" and transform to a cancer cell. In the research group we study genes involved in early development, using Drosophila melanogaster as a model organism. We study regulation and function of genes causing stable silencing of important developmental genes, but also genes whose activity leads to the formation of specific organs, like eyes.
All Polycomb group proteins isolated today exists in both humans and Drosophila, they form similar complexes and biochemical studies show that the complexes in both species contain histone modifying enzymes, like deacetylases, ubiquitin ligases and methylases. This indicates that the Polycomb silencing mechanisms are similar in Drosophila and humans and involve histone modifications and repressive nucleosome/chromatin configuration. There are also indications from PcG gene knock-out mice that the silenced target genes are involved in cell cycle control and tumorigenesis and analyses of gene expression in tumours have further given support for these results. Since Drosophila has many useful tools and properties for studies of gene interactions, knock-out mutant phenotypes and directed over-expression effects in transgenic lines, we will to use this model organism in order to elucidate the function of the Polycomb group proteins in Drosophila, specifically the PRC2 complex subunit Suppressor-of-zeste-12, in order to understand the long-term control of gene regulation and cell proliferation during development. We also study the two paralogous Pax6 genes in Drosophila and their specific regulation and possible functional redundancy.