| 2013 |
The RAWUL domain of PCGF1 binds selectively to the PUFD domain of BCOR (but not to PCGF2/MEL18 or PCGF4/BMI1 RAWUL domains). Crystal structure of the BCOR PUFD–PCGF1 RAWUL complex reveals that PUFD binds the same surfaces as other Polycomb RAWUL interactions, and selectivity is determined by specific residues within these interaction surfaces. |
X-ray crystallography, in vitro binding assays, analytical ultracentrifugation |
Structure |
High |
23523425
|
| 2016 |
PCGF1 and BCORL1 form a heterodimer (via PCGF1 RAWUL and BCORL1 PUFD) that is required for KDM2B recruitment to assemble a minimal four-component PRC1.1 complex (KDM2B/SKP1/BCORL1/PCGF1). The crystal structure shows that BCORL1 PUFD positions residues preceding the PCGF1 RAWUL to create an extended interface unique to PCGF1-containing PRC1.1. BCOR PUFD internal tandem duplications found in pediatric tumors are structurally rationalized by this complex. |
X-ray crystallography, in vitro assembly assays, analytical ultracentrifugation |
Structure |
High |
27568929
|
| 2008 |
NSPc1/PCGF1 stimulates H2A ubiquitination in vivo and in vitro through direct interaction with both RING2 and H2A. NSPc1 cooperates with EZH2-mediated H3K27me3 and Dnmt1-mediated DNA methylation at the HOXA7 promoter; NSPc1 knockdown reduces H2AK119ub and leads to DNA demethylation and Dnmt1 dissociation, while EZH2 depletion abolishes NSPc1 recruitment. |
In vitro ubiquitination assay, co-immunoprecipitation, ChIP, siRNA knockdown, RT-PCR |
Nucleic Acids Research |
High |
18460542
|
| 2018 |
The FBXL10(KDM2B)–RNF68(PCGF1)–RNF2 ubiquitin ligase complex (FRRUC) is rapidly and transiently recruited to DNA damage sites in a PARP1- and TIMELESS-dependent manner. At damage sites FRRUC promotes H2AK119 mono-ubiquitylation, a local decrease of H2A levels, increased H2A.Z incorporation, transcriptional repression, DSB signaling, and homologous recombination repair. FRRUC activity is also required for subsequent proper recruitment of BMI1–RNF2 and MEL18–RNF2 complexes. |
Live-cell imaging, co-immunoprecipitation, laser micro-irradiation, knockdown/knockout with functional readouts (HR repair assays, DSB signaling) |
eLife |
High |
29985131
|
| 2021 |
PCGF1-containing variant PRC1 (PCGF1-PRC1) mediates differentiation-associated transcriptional down-regulation of target genes by depositing H2AK119ub1 and recruiting PRC2. In the absence of PCGF1, both H2AK119ub1 deposition and PRC2 recruitment are disrupted, leading to aberrant expression of target genes during embryoid body differentiation. |
PCGF1 knockout in ESCs, ChIP-seq, RNA-seq, embryoid body differentiation assay |
Nature Communications |
High |
34504070
|
| 2022 |
PCGF1-PRC1 localizes at the replication fork and prevents overloading of activators and chromatin remodeling factors on nascent DNA, thereby mediating proper nucleosome deposition and correct chromatin configurations. This replication-fork function facilitates downstream PRC2-mediated repression of target genes (e.g., Hmga2) and restricts premature myeloid differentiation in hematopoietic stem and progenitor cells. |
PCGF1 conditional KO in HSPCs, iPOND/nascent chromatin capture, ChIP-seq, RNA-seq, differentiation assays |
Nature Communications |
High |
36443290
|
| 2024 |
At the single-molecule level, variant PRC1 containing PCGF1 transiently samples chromatin until reaching a catalytically competent nucleosome-bound state that enables E2 recruitment and ubiquitin transfer to H2AK119. PCGF1-containing PRC1 has lower activity than PCGF4-containing PRC1 because it achieves the catalytically competent state with lower probability. Variant PRC1 shows weak processivity in ubiquitylating neighboring nucleosomes. |
Single-molecule fluorescence microscopy, in vitro chromatin ubiquitylation reconstitution |
bioRxiv (preprint)preprint |
High |
bio_10.1101_2024.10.25.620026
|
| 2005 |
NSPc1/PCGF1 protein localizes predominantly to the nucleus. Its transcriptional repression activity depends on the C-terminal domain and specifically on the PKC phosphorylation site at serine 183; mutation of this site impairs repression activity. |
Subcellular fractionation/immunofluorescence, luciferase reporter assay with deletion/point mutants, Western blot |
FEBS Letters |
Medium |
15620699
|
| 2006 |
NSPc1/PCGF1 represses p21Waf1/Cip1 transcription by binding to the −1357 to −1083 region of the p21 promoter, and this repression is dependent on the retinoic acid response element (RARE) within that region. NSPc1 competes with RA receptors for the RARE element both in vitro and in vivo. |
ChIP, DNA pulldown, luciferase reporter assays, RT-PCR, siRNA knockdown |
Nucleic Acids Research |
Medium |
17088287
|
| 2013 |
Nspc1/PCGF1 directly binds the −1021 to −784 region of the Oct4 promoter and activates Oct4 transcription in a RARE-dependent manner, thereby positively regulating the Oct4-Nanog-Sox2 pluripotency axis in P19 embryonal carcinoma cells. |
ChIP, luciferase reporter assay, dominant-negative analysis, siRNA/overexpression |
Biochemical and Biophysical Research Communications |
Medium |
24113379
|
| 2017 |
NSPc1/PCGF1 promotes cancer stem cell self-renewal in glioma by epigenetically repressing RDH16 through direct binding to the −1073 to −823 region of the RDH16 promoter, reducing all-trans retinoic acid (ATRA) synthesis; RDH16 restoration partially rescues the NSPc1-induced stemness enhancement. |
ChIP, shRNA knockdown, sphere formation assay, xenograft, RT-PCR/Western blot |
Oncogene |
Medium |
28394339
|
| 2015 |
Under endogenous conditions in a neuronal differentiation cell model, PCGF1 physically interacts with all previously reported members of the variant PRC1 complex (including BCOR and KDM2B) and additionally with a pluripotency sub-network including NANOG, OCT4, PATZ1, and DPPA4. PCGF1 knockdown reduces DPPA4 expression at both mRNA and protein levels. |
Affinity purification–mass spectrometry (AP-MS) under endogenous conditions, siRNA knockdown, Western blot |
Scientific Reports |
Medium |
26687479
|
| 2017 |
Pcgf1 loss-of-function in mouse ES cells (CRISPR/Cas9 KO) severely impairs in vitro differentiation while self-renewal is maintained. ChIP shows that Pcgf1 deletion reduces Ring1B and H2AK119ub1 occupancy at target genes, revealing an unexpected positive role of Pcgf1 in gene activation during ES cell lineage specification. |
CRISPR/Cas9 knockout, RNA-seq, ChIP, differentiation assays |
Scientific Reports |
Medium |
28393894
|
| 2024 |
PCGF1 facilitates deposition of H2AK119ub at MHC class I gene promoters to silence MHC-I transcription in tumor cells. The deubiquitinase BAP1 opposes this by removing H2AK119ub, and PCGF1 depletion restores MHC-I expression and T cell-mediated killing of tumor cells. |
Genome-wide CRISPR screen, PCGF1 KO/knockdown, ChIP, T cell cytotoxicity assays in multiple tumor lines |
Journal of Immunology |
Medium |
38088808
|
| 2024 |
PCGF1 inhibits MMP10 transcription by upregulating RING1B/H2AK119ub and EZH2/H3K27me3 marks at the MMP10 promoter in microglia, thereby suppressing NF-κB/MAPK pathway activation and neuroinflammation. |
ChIP, in vivo microglial PCGF1 manipulation, behavioral assays, Western blot |
Molecular Psychiatry |
Medium |
39215186
|
| 2023 |
NSPc1/PCGF1 requires DNMT3a recruitment for maintenance of DNA methylation at the HOXA11 promoter in trophoblast cells; NSPc1 is required for DNMT3a occupancy, and the NSPc1–DNMT3a cooperation represses HOXA11 and promotes trophoblast cell apoptosis. |
ChIP, siRNA knockdown, co-immunoprecipitation, bisulfite sequencing, apoptosis assays |
Acta Biochimica et Biophysica Sinica |
Medium |
36815373
|
| 2023 |
MORC4 interacts physically with PCGF1 (by co-immunoprecipitation) and augments PCGF1's repression of CDKN1A (p21) transcription; MORC4 itself does not substantially suppress CDKN1A activity but potentiates PCGF1's effect. MORC4 is degraded via the ubiquitin-proteasome system by HECW2. |
Co-immunoprecipitation, luciferase reporter assay, siRNA/overexpression, Western blot |
Cancer Gene Therapy |
Low |
36932196
|
| 2021 |
Pcgf1 loss-of-function in zebrafish decreases H3K27me3 at the promoters of Ngn1 and Otx2 and decreases H3K4me3 at the promoters of Pou5f3 and Nanog, implicating Pcgf1 in maintaining specific histone methylation states during early neural tube development. |
Morpholino knockdown in zebrafish, ChIP, RNA-seq in P19 cells |
Frontiers in Cell and Developmental Biology |
Low |
33575252
|
| 2024 |
USP15 deubiquitinates and stabilizes TFAP4, which transcriptionally activates PCGF1; the USP15–TFAP4–PCGF1 axis promotes EMT, invasion, and stemness in colorectal cancer cells. |
Co-immunoprecipitation, dual luciferase reporter assay, oligonucleotide pulldown, ChIP, siRNA knockdown |
Biochemical Pharmacology |
Low |
38801926
|