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Updated: Mar 21, 2026
Chromatin Isolation by RNA Purification ChIRP
Published on: March 25, 2012
The interaction of PRC2 with RNA or chromatin is mutually antagonistic
Manuel Beltran1, Christopher M Yates1, Lenka Skalska1
1UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
Abstract:
Polycomb repressive complex 2 (PRC2) modifies chromatin to maintain genes in a repressed state during development. PRC2 is primarily associated with CpG islands at repressed genes and also possesses RNA binding activity. However, the RNAs that bind PRC2 in cells, the subunits that mediate these interactions, and the role of RNA in PRC2 recruitment to chromatin all remain unclear. By performing iCLIP for PRC2 in comparison with other RNA binding proteins, we show here that PRC2 binds nascent RNA at essentially all active genes. Although interacting with RNA promiscuously, PRC2 binding is enriched at specific locations within RNAs, primarily exon-intron boundaries and the 3' UTR. Deletion of other PRC2 subunits reveals that SUZ12 is sufficient to establish this RNA binding profile. Contrary to prevailing models, we also demonstrate that the interaction of PRC2 with RNA or chromatin is mutually antagonistic in cells and in vitro. RNA degradation in cells triggers PRC2 recruitment to CpG islands at active genes. Correspondingly, the release of PRC2 from chromatin in cells increases RNA binding. Consistent with this, RNA and nucleosomes compete for PRC2 binding in vitro. We propose that RNA prevents PRC2 recruitment to chromatin at active genes and that mutual antagonism between RNA and chromatin underlies the pattern of PRC2 chromatin association across the genome.
Insights
Polycomb repressive complex 2 (PRC2) binds nascent RNA at active genes, contrary to prior beliefs. RNA binding antagonizes PRC2
Area of Science:
- Epigenetics
- Molecular Biology
- Gene Regulation
Background:
- Polycomb repressive complex 2 (PRC2) is crucial for developmental gene repression.
- PRC2 associates with CpG islands at repressed genes and has RNA-binding capabilities.
- The specific RNAs bound by PRC2, mediating subunits, and RNA's role in chromatin recruitment remain largely unknown.
Purpose of the Study:
- To identify RNAs interacting with PRC2 in cells.
- To determine the subunits responsible for PRC2-RNA interactions.
- To elucidate the role of RNA in PRC2's recruitment to chromatin.
Main Methods:
- Individual-nucleotide-resolution crosslinking and precipitation (iCLIP) for PRC2 and other RNA-binding proteins.
- Analysis of PRC2 binding sites on nascent RNA.
- Genetic manipulation of PRC2 subunits.
- In vitro binding assays with RNA and nucleosomes.
Main Results:
- PRC2 binds nascent RNA at nearly all active genes, with enrichment at exon-intron boundaries and 3' UTRs.
- The SUZ12 subunit is sufficient for PRC2's RNA-binding profile.
- PRC2-RNA and PRC2-chromatin interactions are mutually antagonistic.
- RNA degradation promotes PRC2 recruitment to active gene CpG islands.
- RNA and nucleosomes compete for PRC2 binding in vitro.
Conclusions:
- RNA binding by PRC2 occurs promiscuously but is enriched at specific RNA locations.
- The SUZ12 subunit dictates PRC2's RNA binding specificity.
- Contrary to existing models, RNA binding inhibits PRC2's association with chromatin.
- A mutual antagonism between RNA and chromatin governs PRC2's genome-wide distribution.
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