ArticleProceedings of the National Academy of Sciences of the United States of America2012
A core subunit of Polycomb repressive complex 1 is broadly conserved in function but not primary sequence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 122 citations in OpenAlex.
- ZmEMF1a is required for the maintenance of H2Aub and H3K27me3 modifications in maize kernel development.Genome biology · 2026Article
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Evolutionary turnover of key amino acids explains conservation of function without conservation of sequence in transcriptional activation domains.PLoS genetics · 2026Article
- Motifs and chemistry dictate the role of intrinsically disordered regions.Nature cell biology · 2026Article
- Sequence and chemical specificity define the functional landscape of intrinsically disordered regions.Nature cell biology · 2026Article
- Statistical Physics-Based Approaches to Model the Function and Complexation of Disordered Proteins.The journal of physical chemistry. B · 2025Article
- Cross-species rescue reveals sequence requirements for a rapidly evolving intrinsically disordered region.PLoS biology · 2025Article
- EMBRYONIC FLOWER 1 regulates male reproduction by repressing the jasmonate pathway downstream transcription factor MYB26.The Plant cell · 2024Article
- Physics-Based Machine Learning Trains Hamiltonians and Decodes the Sequence-Conformation Relation in the Disordered Proteome.Journal of chemical theory and computation · 2024Article
- Conserved molecular recognition by an intrinsically disordered region in the absence of sequence conservation.Research square · 2024Article
- Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator.Nature communications · 2024Article
- Evolutionary analyses of intrinsically disordered regions reveal widespread signals of conservation.PLoS computational biology · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- A Two-Step Mechanism for Creating Stable, Condensed Chromatin with the Polycomb Complex PRC1.Molecules (Basel, Switzerland) · 2024Article
- Learning functional conservation between human and pig to decipher evolutionary mechanisms underlying gene expression and complex traits.Cell genomics · 2023Article
- Cell type-specific role of CBX2 and its disordered region in spermatogenesis.Genes & development · 2023Article
- Disruption of polyhomeotic polymerization decreases nucleosome occupancy and alters genome accessibility.Life science alliance · 2023Article
- Context-specific Polycomb mechanisms in development.Nature reviews. Genetics · 2022Review
- Conformational buffering underlies functional selection in intrinsically disordered protein regions.Nature structural & molecular biology · 2022Article
- Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning.PLoS computational biology · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Polycomb Group (PcG) proteins mediate heritable gene silencing by modifying chromatin structure. An essential PcG complex, PRC1, compacts chromatin and inhibits chromatin remodeling. In Drosophila melanogaster, the intrinsically disordered C-terminal region of PSC (PSC-CTR) mediates these noncovalent effects on chromatin, and is essential for viability. Because the PSC-CTR sequence is poorly conserved, the significance of its effects on chromatin outside of Drosophila was unclear. The absence of folded domains also made it difficult to understand how the sequence of PSC-CTR encodes its function. To determine the mechanistic basis and extent of conservation of PSC-CTR activity, we identified 17 metazoan PSC-CTRs spanning chordates to arthropods, and examined their sequence features and biochemical properties. PSC-CTR sequences are poorly conserved, but are all highly charged and structurally disordered. We show that active PSC-CTRs--which bind DNA tightly and inhibit chromatin remodeling efficiently--are distinguished from less active ones by the absence of extended negatively charged stretches. PSC-CTR activity can be increased by dispersing its contiguous negative charge, confirming the importance of this property. Using the sequence properties defined as important for PSC-CTR activity, we predicted the presence of active PSC-CTRs in additional diverse genomes. Our analysis reveals broad conservation of PSC-CTR activity across metazoans. This conclusion could not have been determined from sequence alignments. We further find that plants that lack active PSC-CTRs instead possess a functionally analogous PcG protein, EMF1. Thus, our study suggests that a disordered domain with dispersed negative charges underlies PRC1 activity, and is conserved across metazoans and plants.
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