Dynamic Regulation by Polycomb Group Protein Complexes Controls Pattern Formation and the Cell Cycle in Drosophila

Abstract

Polycomb group (PcG) proteins form conserved regulatory complexes that modify chromatin to repress transcription. Here, we report genome-wide binding profiles of PhoRC, the Drosophila PcG protein complex containing the DNA-binding factor Pho/dYY1 and dSfmbt. PhoRC constitutively occupies short Polycomb response elements (PREs) of a large set of developmental regulator genes in both embryos and larvae. The majority of these PREs are co-occupied by the PcG complexes PRC1 and PRC2. Analysis of PcG mutants shows that the PcG system represses genes required for anteroposterior, dorsoventral, and proximodistal patterning of imaginal discs and that it also represses cell cycle regulator genes. Many of these genes are regulated in a dynamic manner, and our results suggest that the PcG system restricts signaling-mediated activation of target genes to appropriate cells. Analysis of cell cycle regulators indicates that the PcG system also dynamically modulates the expression levels of certain genes, providing a possible explanation for the tumor phenotype of PcG mutants.

Drosophila O -GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs ( sxc )

“…PcG proteins regulate many targets, including genes encoding proteins that function throughout development (17,18). Some of the pleiotropic phenotypes of Ogt mutants may thus be a consequence of improper silencing of PcG targets, although our data do not rule out other roles for OGT and O-GlcNAc modification in the many important cellular processes linked to OGT function.…”

“…To determine whether the addition of O-GlcNAc residues by OGT might act in concert with PcG protein binding to downstream target genes, we used an anti-O-GlcNAc antibody for in situ analysis of polytene chromosomes. This antibody was chosen because the available anti-OGT (17,18), and suggests that 1 or more PcG proteins could be candidate substrates. The resolution of in situ hybridization is not sufficient to show that OGT acts at the known sites of PcG protein binding, the PcG response elements (PREs).…”

Gene Silencing and Polycomb Group Proteins: An Overview of their Structure, Mechanisms and Phylogenetics

“…PcG proteins accumulate widely along chromosomes (Decamillis et al, 1992;Zink and Paro, 1989) and are recruited to PREs in association with transcription factors (for a review, see Ringrose and Paro, 2007) and DNA binding proteins such as Pho (Oktaba et al, 2008). In mammals, several transcription factors are involved in the recruitment of PcG proteins (Bracken and Helin, 2009), which has led to conflicting findings about PRE motifs, protein interaction sites that bring together different proteins in multi-protein complexes and locate them within heterochromatin (Brasher et al, 2000).…”

“…Studies addressing the PcG silencing mechanism have provided evidence for the dynamic control of gene expression (Kia et al, 2008;Kwong et al, 2008;Oktaba et al, 2008). Generally, long-term regulation of gene expression is controlled by Pc complexes and, antagonistically, by the trithorax group, through the modulation of chromatin structures and histone modifications.…”

“…genes (Schwartz et al, 2006) and dynamically regulate their expression (Oktaba et al, 2008). For biological activity, PcG proteins need to be part of complexes consisting of core components and associated components.…”