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Mapping dynamic Polycomb group proteins during Drosophila development

April 20, 2006

The developmental passage from a ball of cells to a fruit-fly is a very complicated process involving both temporal and spatial regulation of genes and pathways. All components of this development are equally as important, and understanding how each of them works reveals a little more about whole organism development. In a study published this week in the open-access journal PLoS Biology scientists probe how fly development is regulated by monitoring how the Polycomb group (PcG) proteins (important regulators of gene silencing) bind to regions of chromatin (the twisted up DNA found in the cell) at different developmental stages across Drosophila chromosomes X and 2.

According to the study performed by Nicolas Nîgre, Giacomo Cavalli, and colleagues, the PcG proteins PC and PH vary widely in their distributions from one developmental time-point to the next. Although some of their binding locations were maintained at all times, other PcG protein locations varied considerably, implying that PcGs employ dynamic regulation over time. In fact, adult male flies had the most divergent profile of PcG Response Elements (the region of chromatin where the PcG proteins bind), suggesting that some male-specific development might be regulated by these PcG proteins.

The authors applied a technique known as "ChIP on chip" which identifies matches between the region of chromatin where the protein of interest has bound (via chromatin immunoprecipitation, or ChIP) and the corresponding genomic region on a tiled microarray (or chip) and therefore permits a wider-scale analysis of their binding locations. Over the genomic regions investigated PC and PH almost perfectly co-localize which confirms their presence together in the PcG protein complex. The PcG proteins also bind in clusters implying that more than one PRE must exist in proximate locations and suggests the PcG proteins might employ a variety of gene silencing mechanisms. The researchers also looked at the localization of another protein, GAF, that had previously been seen to co-localize with the PcG proteins. In fact GAF and the PcG proteins do not always co-localize; GAF actually binds to more sites in total than PC and PH. GAF binding sites do not vary over time.

The next steps in better understanding the molecular construction of a fly will be to extend this analysis to the remaining Drosophila chromosomes, across other developmental stages, and in different tissue types. From there, scientists can similarly probe what makes a mammal, and the extent to which these mechanisms are conserved across distant species.

Public Library of Science