A Genetic Screen Identifies Novel Polycomb Group Genes in Drosophila

Abstract

Polycomb group (PcG) genes encode evolutionarily conserved transcriptional repressors that are required for the long-term silencing of particular developmental control genes in animals and plants. PcG genes were first identified in Drosophila as regulators that keep HOX genes inactive in cells where these genes must remain silent during development. Here, we report the results of a genetic screen aimed at isolating novel PcG mutants in Drosophila. In an EMS mutagenesis, we isolated 82 mutants that show Polycomb-like phenotypes in clones in the adult epidermis and misexpression of the HOX gene Ubx in clones in the imaginal wing disc. Analysis of these mutants revealed that we isolated multiple new alleles in most of the already-known PcG genes. In addition, we isolated multiple mutant alleles in each of ten different genes that previously had not been known to function in PcG repression. We show that the newly identified PcG gene calypso is required for the long-term repression of multiple HOX genes in embryos and larvae. In addition, our studies reveal that the Kto/Med12 and Skd/Med13 subunits of the Med12ÁMed13ÁCdk8ÁCycC repressor subcomplex of Mediator are needed for repression of the HOX gene Ubx. The results of the mutant screen reported here suggest that the majority of nonredundant Drosophila genes with strong classic PcG phenotypes have been identified.

Polycomb Repressive Complex 2-Dependent and -Independent Functions of Jarid2 in Transcriptional Regulation in Drosophila

“…It is also possible that at these loci Jarid2 has a more transient association or even that it is less accessible to interact with the antibodies that we have generated. However, our findings are also in agreement with modifier screens that have been performed in Drosophila to identify major regulators of Polycomb group-mediated phenotypes but that were unable to capture Jarid2 (11).…”

Biochemical mechanisms of gene regulation by polycomb group protein complexes

“…A recent systematic genetic screen aimed at isolating Drosophila mutants with PcG phenotypes, identified multiple alleles in most of the already known PcG loci [64]. However, the screen also resulted in the isolation of mutant alleles of genes previously not known to be involved in PcG repression.…”

Histone H2A monoubiquitination and Polycomb repression

“…7 Like Sce, PR-DUB is required for repression of HOX genes both during embryogenesis and during larval development. 7,44 Given that removal of the Sce E3 ligase that catalyzes H2Aub formation results in loss of HOX gene repression, it may seem paradoxical that removal of PR-DUB and the concomitant increase in H2Aub levels results in the same phenotype. In this context, it is important to note that the level of Sce protein itself is unaffected in embryos that lack PR-DUB.…”