Abstract
Polycomb group (PcG) proteins are key regulators in establishing a transcriptional repressive state. Polycomb Repressive Complex 2 (PRC2), one of the two major PcG protein complexes, is essential for proper differentiation and maintenance of cellular identity. Multiple factors are involved in recruiting PRC2 to its genomic targets. In this review, we will discuss the role of DNA sequence, transcription factors, pre-existing histone modifications, and RNA in guiding PRC2 towards specific genomic loci. The DNA sequence itself influences the DNA methylation state, which is an important determinant of PRC2 recruitment. Other histone modifications are also important for PRC2 binding as PRC2 can respond to different cellular states via crosstalk between histone modifications. Additionally, PRC2 might be able to sense the transcriptional status of genes by binding to nascent RNA, which could also guide the complex to chromatin. In this review, we will discuss how all these molecular aspects define a local chromatin state which controls accurate, cell-type-specific epigenetic silencing by PRC2. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.