Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho

Significance How Polycomb group (PcG) proteins are precisely recruited to their target genes remains poorly understood. InDrosophila , PcG proteins are recruited to Polycomb response elements (PREs), composed of binding sites for multiple DNA-binding proteins. To understand how PcG proteins are recruited to and maintained at PREs, we systematically investigated PcG binding, associated H3K27me3, and transcriptome in wild type and mutants for three PRE-binding proteins. We show two factors are essential for high levels of H3K27me3 in PcG domains. Loss of H3K27me3 does not automatically result in gene expression. Different PREs respond differently to the loss of one factor. Many Polycomb domains contain different types of PREs. The diverse and combinatorial nature of PREs contributes to the remarkable resiliency of PcG repression.