Polycomb group genes (PcG) encode a group of about 16 proteins that were first identified in Drosophila as repressors of homeotic genes. PcG proteins are present in all metazoans and are best characterized as transcriptional repressors. In Drosophila, these proteins are known as epigenetic regulators because they remember, but do not establish, the patterned expression state of homeotic genes throughout development. PcG proteins, in general, are not DNA binding proteins, but act in protein complexes to repress transcription at specific target genes. How are PcG proteins recruited to the DNA? In Drosophila, there are specific regulatory DNA elements called Polycomb group response elements (PREs) that bring PcG protein complexes to the DNA. Drosophila PREs are made up of binding sites for a complex array of DNA binding proteins. Functional PRE assays in transgenes have shown that PREs act in the context of other regulatory DNA and PRE activity is highly dependent on genomic context. Drosophila PREs tend to regulate genes with a complex array of regulatory DNA in a cell or tissue-specific fashion and it is the interplay between regulatory DNA that dictates PRE function. In mammals, PcG proteins are more diverse and there are multiple ways to recruit PcG complexes, including RNA-mediated recruitment. In this review, we discuss evidence for PREs in vertebrates and explore similarities and differences between Drosophila and vertebrate PREs.
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