The role of polycomb group genes in mitosis in Drosophila melanogaster

In Drosophila, the Polycomb Group (PcG) of epigenetic regulators have classically been studied as chromatin regulatory proteins which maintain the repressed state of Hox genes during development, thereby maintaining the correct patterning of the anteroposterior axis. Though the mechanism of PcG-mediated inheritance is not yet known, it likely involves co-ordination with cell cycle regulators to ensure faithful transmission of repressed Hox states during cell division, and thus maintenance of the body plan. So far, very little evidence has linked the PcG to cell cycle progression. Recently, Lupo et al. (2001) demonstrated that a PcG mutant, polyhomeotic, exhibits chromatin bridges at anaphase, and an isoform of Polyhomeotic protein co-immunoprecipitates with cell cycle regulators Barren and Topoisomerase II. I have characterized mitotic defects in early embryos of a subset of PcG mutants and demonstrate that segregation defects and other cell cycle progression defects are common to many PcG mutants. This suggests that the PcG as a whole has a role in cell cycle progression. Characterization of the segregation defects focused on mutants of the polyhomeotic proximal gene (ph-p) and revealed that the chromatin bridges are restricted to chromatid arms, and likely arise during S-phase. PH-P protein partially co-localizes with the S-phase regulators Geminin and PCNA, further suggesting an S-phase role for PH-P. In early embryos, the chromatin bridges present a physical barrier to PH-P oscillation during the cell cycle, such that normal PH-P reassociation with chromatin following anaphase is delayed. To assess whether cell cycle progression affects PcG-mediated silencing during later development, I performed a number of genetic interaction assays between PcG mutants and mutants of known cell cycle regulators. All cell cycle mutants which themselves exhibit segregation defects enhance the adult homeotic phenotypes of PcG mutants. I propose a model which describes an S-phase role for PH-P, and suggests that cell cycle progression is a crucial component of epigenetic inheritance.Science, Faculty ofZoology, Department ofGraduat