Gene regulation in Drosophila melanogaster
Analysis of gene silencing in Drosophila melanogaster.
Drosophila Polycomb Group (PcG) complexes are responsible for the maintenance of the repressed state of specific genes, e.g. the homeotic genes. The genes in the Antennapedia and Bithorax complexes are activated in the early embryo by products of segmentation genes. Transient, localised activators and repressors determine the segmental domains of expression of each homeotic gene.
The specific expression patterns must, however, be remembered for the rest of development and this is where PcG proteins comes in. These complexes bind to regulatory regions, called Polycomb Response Elements (PREs) and thereby maintain a silenced state, while other protein complexes containing the Trithorax protein (TRX) mediate persistence of the active state. Which state the gene will be in, depends on the activity of the promoter at the blastoderm stage. There are two PcG complexes described; PRC1, consisting of Polycomb, Polyhomeotic, Pleiohomeotic and GAGA factors, and the E(z)/Esc (Enhancer of zeste/extra sex combs) complex, which also contains p55 and Rpd3 subunits.We have isolated a gene encoding another PcG protein, Suppressor-of-zeste-12 (Su(z)12) which is a subunit in the E(Z)/Esc complex. Mutants in the Su(z)12 gene exhibit very strong homeotic transformations and SU(Z)12 function is required throughout development to maintain the repressed state of the homeotic genes.The Su(z)12 protein is highly conserved in vertebrates and is related to at least three Arabidopsis proteins. Our current research concerns the role of Su(z)12 in the silencing complex and the function of the various conserved protein domains.
Regulation of toy; a Pax-6 gene in Drosophila melanogaster
There are two Pax-6 genes in Drosophila. They encode transcription factors that are important for the correct development of e.g. head structures of flies, a function that is conserved also in humans. One of the Pax-6 genes, toy (twin-of-eyeless), is expressed during early embryonic development and its product initiates the transcription of the second Pax-6 gene, eyeless (ey), by binding to a specific enhancer element in the first ey intron. Complete loss of Toy results in headless flies that die during the pupal stage (see Figure). Loss of ey cause eyeless flies, while weaker alleles give a small eye phenotype.Mutations in the mammalian homologs, the mouse Small eyes gene and the human Aniridia gene, also affect eye development. Homozygous mutant mice lack eye formation and heterozygous mutations of the human Pax-6 gene cause various forms of congenital eye abnormalities referred to as aniridia and Peters' anomaly. We are currently investigating the transcriptional regulation of the Drosophila toy gene by use of the GAL4/UAS system.