Polycombregulated

Polycomb-regulated describes genes or genomic regions whose transcription is controlled by Polycomb group (PcG) protein complexes, notably PRC1 and PRC2. These complexes mediate heritable transcriptional repression through histone modifications, including PRC2-catalyzed trimethylation of histone H3 at lysine 27 (H3K27me3) and PRC1-mediated monoubiquitination of histone H2A at lysine 119 (H2AK119ub1). The combined activities promote a repressive chromatin state and reduced accessibility of the transcriptional machinery.

Many Polycomb-regulated loci are developmentally regulated. In embryonic stem cells, a subset of PcG targets displays bivalent chromatin marks, with H3K27me3 and H3K4me3, keeping genes poised for activation upon differentiation while remaining silent in the pluripotent state.

Recruitment and maintenance of Polycomb repression are complex and context-dependent. PcG targeting involves multiple components and signals, including CpG island promoters, noncoding RNAs, and transcription factors. PRC2 recruitment can be guided by existing histone marks or interacting proteins such as JARID2 and AEBP2, while PRC1 recognizes H3K27me3 via CBX subunits and can further compact chromatin. Dynamic regulation allows progressive silencing or release during development and in response to signaling.

Polycomb-regulated genes control key developmental decisions and stem cell identities. Dysregulation of PcG function, such as EZH2 overexpression or PRC1 alterations, is linked to cancer and developmental disorders, reflecting the importance of precise PcG-mediated repression for organismal homeostasis.