Abstract
Polycomb Group (PcG) proteins are epigenetic repressors essential for control of development and cell differentiation. They form multiple complexes of which PRC1 and PRC2 are evolutionary conserved and obligatory for repression. The targeting of PRC1 and PRC2 is poorly understood and was proposed to be hierarchical and involve tri-methylation of histone H3 (H3K27me3) and/or monoubiquitylation of histone H2A (H2AK118ub). Here, we present a strict test of this hypothesis using the Drosophila model. We discover that neither H3K27me3 nor H2AK118ub is required for targeting PRC complexes to Polycomb Response Elements (PREs). We find that PRC1 can bind PREs in the absence of PRC2 but at many PREs PRC2 requires PRC1 to be targeted. We show that one role of H3K27me3 is to allow PcG complexes anchored at PREs to interact with surrounding chromatin. In contrast, the bulk of H2AK118ub is unrelated to PcG repression. These findings radically change our view of how PcG repression is targeted and suggest that PRC1 and PRC2 can communicate independently of histone modifications.
Highlights
Polycomb Group (PcG) proteins are evolutionarily conserved transcriptional regulators essential for development of all complex plants and animals
Both Psc/Su(z)2 and Su(z)12 proteins are essential for PcG repression and flies homozygous for corresponding loss-offunction mutations die during embryogenesis [38,39], the mutant cells are viable and proliferate in culture
We obtained an experimental system that avoided the redundancy of mammalian PcG group family, provided large quantities of material for biochemical experiments and allowed us to assay the effect of the loss of individual PcG complexes without simultaneous activation of target genes by developmental enhancer factors
Summary
Polycomb Group (PcG) proteins are evolutionarily conserved transcriptional regulators essential for development of all complex plants and animals. A targeting based on combinatorial interactions provides a way to attenuate the repression of target genes in cells where those must remain active It raises the question of how the recruitment of the PRC complexes is coordinated. The studies from the Klose and Brockdorff labs showed that in mouse embryonic stem cells, ubiquitylation of H2AK119 by a RING2-PCGF1-KDM2B complex is necessary and sufficient to recruit PRC2 and H3K27me to multiple target genes [22,33]. This supports the role of H2AK119ub as a key component of the recruitment hierarchy. Our results indicate that there are alternative ways to target PcG repression to genes and suggest that PRC1 and PRC2 communicate independently of histone modifications
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