| 2002 |
MBLR (PCGF6) is a RING finger protein that directly interacts with Ring1B via its RING finger domain, acts as a transcriptional repressor in transfected cells, localizes to the nucleoplasm in interphase and diffuse cytoplasm in mitotic cells, and is specifically phosphorylated at serine 32 during mitosis, most likely by CDK7. |
In vitro biochemical interaction assay, immunocytochemistry, transfection-based transcriptional repressor assay, cell-cycle phosphorylation analysis |
Genes to cells |
Medium |
12167161
|
| 2007 |
PCGF6 (Ring6a/MBLR) is a component of a native JARID1d demethylase complex in human cells; it directly interacts with the H3K4 trimethyl demethylase JARID1d and regulates its enzymatic activity toward trimethyl H3K4. Both proteins co-occupy the Engrailed 2 gene promoter and regulate its expression and H3K4 methylation levels. |
Native complex isolation/co-immunoprecipitation from human cells, direct interaction mapping, in vitro demethylase activity assay with PCGF6, ChIP at the Engrailed 2 locus, RNAi depletion |
Cell |
High |
17320162
|
| 2014 |
Pcgf6 knockdown in mouse ESCs decreases expression of pluripotency genes and de-represses mesodermal- and spermatogenesis-specific genes, and Pcgf6 can replace Sox2 in the generation of germline-competent iPSCs, establishing a non-redundant role in pluripotency maintenance. |
shRNA knockdown in mouse ESCs, gene expression analysis, hematopoietic differentiation assays, iPSC reprogramming with factor substitution |
Stem cells |
Medium |
25187489
|
| 2016 |
PCGF6 associates with the H3K4me3 demethylase JARID1c in dendritic cells and together they negatively regulate H3K4me3 levels; rapid downregulation of PCGF6 upon stimulation is necessary to permit full DC activation, and PCGF6 silencing enhances both spontaneous and stimulated DC activation. |
Co-immunoprecipitation (PCGF6–JARID1c association), ChIP (H3K4me3 levels), siRNA silencing with DC activation readouts |
Cell reports |
Medium |
27498878
|
| 2016 |
In mouse ESCs, Pcgf6 acts as a positive transcriptional regulator binding predominantly to promoters with active chromatin marks; knockdown reduces expression of Oct4, Sox2, and Nanog, while overexpression prevents their downregulation and impairs differentiation. The genomic binding profile of Pcgf6 resembles trithorax group proteins rather than canonical PRC1/PRC2. |
ChIP-seq (binding profile), shRNA knockdown, overexpression, gene expression analysis in mouse ESCs |
Scientific reports |
Medium |
27247273
|
| 2017 |
PCGF6 forms a non-canonical PRC1 complex (PCGF6-PRC1) with RING1A/B and E2F6-associated factors; this complex represses germ cell-related gene promoters in mouse ESCs by recruiting RING1B and mediating H2AK119 mono-ubiquitination. The MAX/MGA heterodimer recruits PCGF6 to target loci, linking sequence-specific recognition to PRC1-dependent silencing. |
Conditional Pcgf6 knockout in mouse ESCs, ChIP-seq (PCGF6, RING1B, H2AK119ub1), co-immunoprecipitation (PCGF6–MAX/MGA), RNA-seq, embryo phenotyping |
eLife |
High |
28304275
|
| 2017 |
CRISPR-Cas9 deletion of Pcgf6 in mouse ESCs causes severe self-renewal defects, de-repression of spermatogenesis/differentiation genes, and dramatically reduced PRC1.6 binding to target chromatin without loss of H2AK119ub1, indicating Pcgf6 is specifically required for PRC1.6 chromatin recruitment in an H2AK119ub1-independent manner. |
CRISPR-Cas9 knockout in mouse ESCs, ChIP (H2AK119ub1, PRC1.6 components), RNA-seq, self-renewal assays |
The Journal of biological chemistry |
High |
28049731
|
| 2019 |
PCGF6 is recruited by OCT4 to super-enhancer regions upstream of cell cycle-associated genes in mouse ESCs, and activates these genes by regulating super-enhancer–promoter chromatin interactions in 3D, as shown by co-localization with OCT4, promoter capture Hi-C, and gene expression analysis. |
ChIP-seq (PCGF6, OCT4), promoter capture Hi-C, gene expression analysis in ESCs |
Protein & cell |
Medium |
31041782
|
| 2020 |
PCGF6 co-localizes with G9A/GLP histone methyltransferase and HDAC1/2 on promoters of germ cell-related genes in mouse ESCs; recruitment of G9A/GLP and HDAC1/2 to these promoters depends on PCGF6 binding, and their presence correlates with H3K9 methylation and reduced histone acetylation. Pcgf6-deficient mice show partial embryonic lethality and reduced fertility, with robust de-repression of germ cell-related genes in somatic tissues. |
Co-immunoprecipitation, ChIP (G9A, GLP, HDAC1/2, H3K9me, H3K4me3), RNA-seq, Pcgf6 knockout mice, immunohistochemistry |
The Journal of biological chemistry |
High |
32482889
|
| 2022 |
In human PSCs, PCGF6 directly interacts with MYC and together they co-occupy a distal regulatory element of SOX2 to activate SOX2 expression; PCGF6 depletion impairs neuroectoderm differentiation and de-represses WNT/β-catenin signaling, promoting mesendoderm fate, while SOX2 overexpression rescues the neuroectoderm phenotype. |
Co-immunoprecipitation (PCGF6–MYC), ChIP (co-occupancy at SOX2 distal enhancer), genomic deletion of SOX2-regulatory element, PCGF6 shRNA depletion, SOX2 rescue overexpression, transcriptome analysis |
Nature communications |
High |
35933409
|
| 2023 |
In papillary RCC cells, PCGF6 interacts with MAX and KDM5D to form a complex; MAX recruits PCGF6 and KDM5D to the CpG island of the MAZ promoter, facilitating H3K4 histone demethylation and hypomethylation, thereby activating MAZ expression, which in turn upregulates CDK4 to drive tumor cell proliferation. |
Co-immunoprecipitation (PCGF6–MAX–KDM5D complex), ChIP (KDM5D, MAX at MAZ promoter), bisulfite sequencing (CpG methylation), overexpression/knockdown with proliferation assays |
Epigenetics & chromatin |
Medium |
36890610
|
| 2024 |
In mouse intestinal epithelium, PCGF6 regulates Tuft cell differentiation independently of H2AK119ub1 deposition and RING1A/B; PCGF6 chromatin occupancy extends outside Polycomb repressive domains to unique promoter and distal regulatory elements through MGA-mediated E-BOX recognition, and involves H3K9me2 deposition at target promoters. PCGF6 inactivation causes autonomous accumulation of Tuft cells not phenocopied by RING1A/B loss. |
Conditional Pcgf6 knockout in mouse intestinal epithelium, ChIP-seq (PCGF6, H2AK119ub1, H3K9me2), comparison with RING1A/B knockout phenotype, MGA co-occupancy analysis |
Developmental cell |
High |
38228142
|