GO:0035102 PRC1 complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035102 (PRC1 complex) is a cellular_component term describing a multiprotein complex that monoubiquitinates histone H2A at lysine 118 in Drosophila or lysine 119 in mammals.
• PRC1 exists as multiple biochemically distinct subcomplexes (PRC1.1-PRC1.6) with different subunit compositions and genomic targeting mechanisms.
• Canonical PRC1 contains a RING1-family E3 ligase (RING1A/RING1B) and a PCGF paralog, plus CBX and PHC proteins that read H3K27me3 and compact chromatin.
• PRC1 maintains stable long-term transcriptional repression and participates in chromatin remodeling, working together with PRC2-mediated H3K27me3.
• PRC1 subunits are recurrently altered in cancers including ovarian cancer, and PRC1.1 disruption enhances bone remodeling in vivo.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of PRC1 subunit function in disease and development.
Description
The PRC1 complex (GO:0035102) is a multiprotein assembly that mediates monoubiquitination of histone H2A at lysine 118 in Drosophila or lysine 119 in mammals, and it is required for stable long-term maintenance of transcriptionally repressed states and for chromatin remodeling. It is one of the two major Polycomb repressive complexes, alongside PRC2, and the two cooperate to establish heritable gene silencing across cell divisions. Because PRC1 controls developmental gene programs and cell-fate decisions, its subunits are intensely studied in stem cell biology, differentiation, and cancer. PRC1 is not a single uniform entity. Biochemical and proteomic studies have defined at least six variant PRC1 complexes (PRC1.1 to PRC1.6) that share a core RING1-PCGF catalytic module but differ in accessory subunits and targeting mechanisms. This diversity allows PRC1 to be recruited to distinct genomic loci, including promoters and CpG-rich regions, and to cooperate with context-specific silencing machineries such as the HUSH complex. For researchers, GO:0035102 provides a controlled vocabulary anchor for annotating proteins, complexes, and experimental perturbations. Understanding PRC1 composition, assembly, and regulation is essential for interpreting chromatin immunoprecipitation, proteomics, and functional genomics data, and for designing CRISPR models that test causality of individual subunits in disease.
PRC1 complex At A Glance
| GO ID | GO:0035102 |
|---|---|
| GO term | PRC1 complex |
| Ontology | cellular_component |
| Synonym | Polycomb repressive complex 1 |
| Major function | Monoubiquitination of histone H2A at lysine 118 (Drosophila) or lysine 119 (mammals); stable maintenance of transcriptional repression; chromatin remodeling |
| Representative subunits | RING1A/RING1B, PCGF paralogs, CBX proteins, PHC proteins, and variant-specific subunits |
| Complex variants | PRC1.1-PRC1.6, differing in PCGF and accessory subunits |
| Associated mark | H2AK119ub1, which cooperates with PRC2-mediated H3K27me3 |
| Disease relevance | Recurrently implicated in cancers such as ovarian cancer and in bone remodeling |
What Is GO:0035102?
In the Gene Ontology, GO:0035102 (PRC1 complex) is a cellular_component term defined as a multiprotein complex that mediates monoubiquitination of lysine residues of histone H2A (lysine-118 in Drosophila or lysine-119 in mammals). The complex is required for stable long-term maintenance of transcriptionally repressed states and is involved in chromatin remodeling. Its synonym is Polycomb repressive complex 1.
Why Is PRC1 complex Important in Cell Biology?
PRC1 is a central effector of Polycomb-mediated gene silencing and a key regulator of developmental gene programs, stem cell identity, and differentiation. Because it catalyzes H2AK119ub1 and compacts chromatin, PRC1 directly shapes the epigenetic landscape that determines whether genes remain off or become activated. Its subunit diversity allows context-specific targeting, including promoter-specific silencing in partnership with the HUSH complex. Dysregulation of PRC1 subunits is linked to cancer and other diseases, making the complex a high-value target for functional genomics and therapeutic hypothesis testing.
• PRC1 maintains stable long-term transcriptional repression, a prerequisite for correct developmental gene regulation.
• It catalyzes H2AK119ub1, a histone mark that cooperates with PRC2-mediated H3K27me3.
• Variant PRC1 complexes (PRC1.1-PRC1.6) provide combinatorial targeting to distinct genomic loci.
• PRC1.6 localizes with the HUSH complex for promoter-specific silencing, linking PRC1 to repeat and transgene silencing.
• PRC1 subunits are recurrently altered in ovarian cancer and other malignancies.
• Targeted disruption of PRC1.1 enhances bone remodeling, showing physiological relevance beyond development.
• PRC1 is essential for chromatin remodeling and for propagating repressed states through cell division.
• CRISPR-based perturbation of PRC1 subunits enables causal testing of gene-disease hypotheses.
PRC1 complex: Components, Assembly and Research Methods
Biological process: What Happens During PRC1 complex?
In simple terms: PRC1 acts like a molecular switch that keeps certain genes turned off and helps that off-state persist as cells divide.
PRC1 mediates monoubiquitination of histone H2A at lysine 118 (Drosophila) or lysine 119 (mammals), a modification associated with transcriptional repression. The complex is required for stable long-term maintenance of transcriptionally repressed states and is involved in chromatin remodeling. PRC1 functions in concert with PRC2, which deposits H3K27me3, and the two complexes cooperate to establish heritable silencing. Variant PRC1 complexes can be recruited to distinct loci, including promoters and CpG-rich regions, and PRC1.6 partners with the HUSH complex for promoter-specific silencing.
Cellular component: Structure and Composition of PRC1 complex
In simple terms: PRC1 is built from a core enzymatic engine plus interchangeable accessory parts that decide where it goes.
Canonical PRC1 contains a RING1-family E3 ubiquitin ligase (RING1A or RING1B) paired with a PCGF paralog, which together form the catalytic core. Accessory subunits include CBX proteins that read H3K27me3 and PHC proteins that contribute to chromatin compaction. Variant PRC1 complexes (PRC1.1-PRC1.6) share the RING1-PCGF module but differ in PCGF paralog and accessory subunits, generating functional diversity. In plants, PRC1 composition and function have also been characterized, underscoring evolutionary conservation.
Molecular function: Catalytic mechanism and cofactors
In simple terms: The RING1-PCGF module attaches a small ubiquitin tag to histone H2A, marking chromatin for repression.
The RING1-PCGF heterodimer provides the E3 ubiquitin ligase activity that monoubiquitinates histone H2A at lysine 118/119. This H2AK119ub1 mark is a hallmark of PRC1 activity and is mechanistically linked to transcriptional repression and chromatin remodeling. PRC1 activity is coordinated with PRC2-mediated H3K27me3, and the two marks can reinforce each other to stabilize repressed states. Variant complexes can be targeted independently of H3K27me3, allowing context-specific repression.
Regulation and targeting of PRC1
In simple terms: Different PRC1 versions are sent to different places in the genome by their accessory subunits.
PRC1 targeting is mediated by accessory subunits and by reader domains that recognize histone marks and DNA features. PRC1.6 localizes on chromatin with the HUSH complex for promoter-specific silencing, illustrating how a variant complex can be directed to specific loci. The spatiotemporal control of germline-specific genes by PRC1.6 further demonstrates context-dependent regulation. Cooperation with PRC2 and with other silencing factors shapes the repressive landscape.
Key Genes Involved in GO:0035102 PRC1 complex
The following genes encode core and variant subunits of the PRC1 complex (GO:0035102) and are commonly studied in functional genomics and disease research.
| Gene | Major Role | Research Relevance |
|---|---|---|
| RING1 | E3 ubiquitin ligase core subunit of PRC1 | Catalytic activity and H2AK119ub1 deposition |
| RNF2 (RING1B) | E3 ubiquitin ligase core subunit of PRC1 | Central to PRC1-mediated repression and cancer studies |
| PCGF1 | Defines PRC1.1 variant | PRC1.1 disruption enhances bone remodeling |
| PCGF2 (MEL18) | PCGF paralog in PRC1 variants | Variant complex composition and targeting |
| PCGF3 | Defines PRC1.3 variant | Variant-specific targeting and silencing |
| PCGF4 (BMI1) | PCGF paralog in canonical PRC1 | Widely studied in cancer and stem cell biology |
| PCGF5 | Defines PRC1.5 variant | Variant complex function |
| PCGF6 | Defines PRC1.6 variant | PRC1.6-HUSH promoter silencing and germline gene control |
| CBX2 | Chromobox reader of H3K27me3 | Canonical PRC1 recruitment and chromatin compaction |
| CBX4 | Chromobox reader and SUMO-related functions | Canonical PRC1 regulation |
| CBX6 | Chromobox reader | Canonical PRC1 targeting |
| CBX7 | Chromobox reader | Canonical PRC1 and cancer biology |
| CBX8 | Chromobox reader | Canonical PRC1 targeting |
| PHC1 | Polyhomeotic subunit | Chromatin compaction and repression |
| PHC2 | Polyhomeotic subunit | Chromatin compaction and repression |
| PHC3 | Polyhomeotic subunit | Chromatin compaction and repression |
| KDM2B | Accessory factor for PRC1.1 targeting | CpG-rich recruitment of variant PRC1 |
How Is PRC1 complex Regulated?
PRC1 activity and targeting are regulated at multiple levels. Accessory subunits and reader domains determine recruitment to specific chromatin contexts, and variant complexes can be targeted independently of H3K27me3. PRC1.6 localizes with the HUSH complex for promoter-specific silencing, showing that partnering with other machineries directs repression. The spatiotemporal control of germline-specific genes by PRC1.6 illustrates developmental regulation. Coordination with PRC2-mediated H3K27me3 reinforces stable repression.
PRC1 complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PCGF1 | Bone remodeling | Knockout and knock-in models to test PRC1.1 disruption |
| PCGF6 | Promoter-specific silencing via HUSH | Knockout and tagged knock-in to map PRC1.6 localization |
| RNF2 (RING1B) | Ovarian cancer and other malignancies | Knockout and point-mutation models to test catalytic activity |
| BMI1 (PCGF4) | Cancer and stem cell biology | Overexpression and knockout models |
| CBX7 | Cancer biology | Knockout and overexpression models |
PRC1 in ovarian cancer
A scoping literature review indicates that PRC1 subunits are recurrently implicated in ovarian cancer biology, supporting their study as potential biomarkers and therapeutic targets. Because PRC1 maintains repressive states, its dysregulation can alter gene programs that drive tumorigenesis.
PRC1.1 and bone remodeling
Targeted disruption of the PRC1.1 complex enhances bone remodeling in vivo, demonstrating that specific PRC1 variants have physiological roles beyond classical developmental silencing. This finding motivates functional studies of PCGF1-containing complexes in skeletal biology.
PRC1.6, HUSH, and promoter silencing
PRC1.6 localizes on chromatin with the HUSH complex for promoter-specific silencing, linking PRC1 to silencing of specific promoters and to control of germline-specific genes. Dysregulation of such silencing mechanisms can contribute to disease-relevant gene activation.
From PRC1 complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a PRC1 subunit required for repression? | CRISPR knockout of the subunit followed by RNA-seq |
| Is catalytic activity of RING1B required? | Point mutation of the catalytic residue in RING1B |
| Where does PRC1.6 bind? | Tagged knock-in of PCGF6 for ChIP-seq |
| Does PRC1.1 disruption affect bone? | Knockout mouse or cell model of PCGF1 |
| Does overexpression drive transformation? | Overexpression of BMI1 or CBX7 in cell models |
| Which genes are silenced by PRC1? | Knockout plus RNA-seq and ChIP-seq |
How to Study the PRC1 complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| ChIP-seq | Genomic binding of PRC1 subunits and H2AK119ub1 | Mapping repressed loci |
| RNA-seq | Transcriptional changes after perturbation | Identifying PRC1-repressed genes |
| Mass spectrometry | Subunit composition of PRC1 complexes | Defining variant complexes |
| Western blot | H2AK119ub1 levels | Measuring catalytic activity |
| CRISPR knockout | Loss-of-function phenotypes | Testing subunit requirement |
| CRISPR knock-in | Tagged endogenous subunits | Localization and interaction studies |
| Overexpression | Gain-of-function effects | Modeling oncogenic roles |
| Bioinformatics analysis | Integration of multi-omics data | Prioritizing PRC1 targets |
Chromatin immunoprecipitation and sequencing
ChIP-seq against PRC1 subunits or H2AK119ub1 maps genomic binding and repression domains, and is widely used to define PRC1 target loci.
Transcriptomics after perturbation
RNA-seq after CRISPR knockout or knockdown of PRC1 subunits identifies genes whose repression depends on the complex.
Proteomics and complex purification
Affinity purification and mass spectrometry define subunit composition of canonical and variant PRC1 complexes.
Functional assays for H2AK119ub1
Western blotting and quantitative assays for H2AK119ub1 measure PRC1 catalytic activity after perturbation.
How CRISPR Can Be Used to Study GO:0035102 PRC1 complex
Knockout
CRISPR knockout of PRC1 subunits such as PCGF1 or RNF2 enables loss-of-function studies of repression and disease phenotypes.
Point Mutation
Point mutations in the catalytic domain of RING1A/RING1B allow separation of enzymatic activity from scaffolding functions.
Knock-in
Tagged knock-in of subunits such as PCGF6 supports ChIP-seq and interaction studies at endogenous loci.
Overexpression
Overexpression of PRC1 subunits like BMI1 or CBX7 models gain-of-function contributions to cancer.
How EDITGENE Supports PRC1 complex Research
Researchers studying PRC1 complex-related genes often need to determine whether a candidate gene is causally involved in repression, development, or disease, and CRISPR-based models provide the most direct route to that answer.
Contact EDITGENE today to design your custom CRISPR model for PRC1 complex research.
Frequently Asked Questions About PRC1 complex
What is the PRC1 complex?
The PRC1 complex (GO:0035102) is a multiprotein complex that monoubiquitinates histone H2A at lysine 118 in Drosophila or lysine 119 in mammals and maintains stable transcriptional repression.
What genes are involved in the PRC1 complex?
Core and variant subunits include RING1, RNF2 (RING1B), PCGF1-PCGF6, CBX2-CBX8, PHC1-PHC3, and accessory factors such as KDM2B.
What does PRC1 do in the cell?
PRC1 catalyzes H2AK119ub1, compacts chromatin, and maintains long-term repression of developmental and other genes.
How is PRC1 different from PRC2?
PRC2 deposits H3K27me3, while PRC1 monoubiquitinates H2A; the two complexes cooperate to stabilize repression.
What are PRC1 variants?
PRC1.1 to PRC1.6 are variant complexes that share a RING1-PCGF core but differ in accessory subunits and targeting.
Is PRC1 involved in cancer?
Yes, PRC1 subunits are recurrently implicated in cancers such as ovarian cancer.
What is PRC1.6?
PRC1.6 is a variant complex that localizes with the HUSH complex for promoter-specific silencing.
Can CRISPR be used to study PRC1?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to study PRC1 subunit function.
What histone mark does PRC1 deposit?
PRC1 deposits H2AK119ub1, monoubiquitination of histone H2A at lysine 118/119.
Why is PRC1 important for development?
PRC1 maintains stable repression of developmental genes, which is essential for correct cell-fate decisions.
Conclusion
The PRC1 complex (GO:0035102) is a central epigenetic regulator that monoubiquitinates histone H2A and maintains stable transcriptional repression through multiple variant complexes. Its subunits are implicated in cancer and bone remodeling, making it a high-priority target for functional genomics. CRISPR-based knockout, point-mutation, knock-in, and overexpression models provide the tools needed to dissect PRC1 biology and translate findings into disease insights.
References
- 1. Xing L et al.. 2025. Targeted disruption of PRC1.1 complex enhances bone remodeling.. Nat Commun 16(1):4294 PMID: 40341537
- 2. Rodríguez TC et al.. 2024. PRC1.6 localizes on chromatin with the human silencing hub (HUSH) complex for promoter-specific silencing.. bioRxiv PMID: 39026796
- 3. Gil J et al.. 2014. PRC1 complex diversity: where is it taking us?. Trends Cell Biol 24(11):632-41 PMID: 25065329
- 4. Blackledge NP et al.. 2021. The molecular principles of gene regulation by Polycomb repressive complexes.. Nat Rev Mol Cell Biol 22(12):815-833 PMID: 34400841
- 5. Floyd J et al.. 2024. Polycomb Repressor Complex 1 (PRC1) in ovarian cancer: A scoping literature review.. Crit Rev Oncol Hematol 202:104456 PMID: 39033867
- 6. Margueron R et al.. 2011. The Polycomb complex PRC2 and its mark in life.. Nature 469(7330):343-9 PMID: 21248841
- 7. Molitor A et al.. 2013. The polycomb complex PRC1: composition and function in plants.. J Genet Genomics 40(5):231-8 PMID: 23706298
- 8. Sun XW et al.. 2019. [Controlling the spatiotemporal expression of germ line specific genes by PRC1.6 complex].. Yi Chuan 41(4):271-284 PMID: 30992249
