Chromatin binding and transcriptional regulation by PRCs

Several molecular mechanisms contribute to the correct genomic targeting of PRCs. Despite the years of studies of transcription factors, non-coding RNAs, and specific DNA features, no clear cause for mammalian PRC recruitment has been identified, although PRCs have been found to bind CpG-rich promoters of non-transcribed genes. Non-core subunits of PRC1 and PRC2 have been shown to guide target site specificity through direct chromatin interactions, strengthened by chromatin-interactions from core subunits. Some studies suggest that non-coding RNAs may be involved in recruiting PRCs to specific loci. Conversely, several studies indicate that RNA transcripts counteract PRC binding by competing for DNA binding surface, thereby providing a ‘sensing mechanism’ to explain selective recruitment of PRCs to non-transcribed genes¹.

PRC binding and histone modifications are suggested to confer transcriptional repression via various mechanisms, including prevention RNA polymerase II binding or release, chromatin compaction, or co-transcriptional RNA degradation. Repression depends on the catalytic activities of both PRC1 and PRC2, which may well vary in distinct cell types, developmental stages, and genomic contexts. However, the relative contributions of each complex and modification remain to be understood².

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References

1. Laugesen, A., Hojfeldt, J. W., Helin, K. Molecular mechanisms directing PRC2 recruitment and H3K27 methylation Mol Cell 74 ,8-18 (2019)
2. Di Croce, L., Helin, K. Transcriptional regulation by polycomb group proteins Nat Struct Mol Biol 20 ,1147-1155 (2013)