| 2009 |
Pygo2 facilitates trimethylation of histone H3 at K4 (H3K4me3), both globally and at Wnt/β-catenin target loci, via direct binding to K4-methyl histone H3 and recruiting histone H3 K4 methyltransferase complexes, thereby expanding mammary epithelial progenitor cells. |
Gene ablation (complete and epithelia-specific knockout in mice), chromatin immunoprecipitation, direct binding assays to K4-methyl H3, recruitment of H3K4 methyltransferase complexes, mammary transplantation/regeneration assays |
The Journal of cell biology |
High |
19487454
|
| 2008 |
Pygo2 is expressed in elongating spermatids during chromatin remodeling and, independently of β-catenin, controls histone H3 hyperacetylation patterning and expression of post-meiotic genes (protamines, transition protein 2, H1fnt) required for chromatin condensation during spermiogenesis; loss of Pygo2 function causes spermiogenesis arrest and male infertility. |
Hypomorphic allele mouse model, histological analysis of spermiogenesis, immunostaining for histone H3 hyperacetylation, RT-PCR/expression analysis of post-meiotic genes |
Developmental biology |
High |
18614164
|
| 2007 |
Pygo1 and Pygo2 function as quantitative modulators (not absolute requirements) of canonical Wnt signaling during kidney development; double knockout reduces BAT-gal Wnt reporter activity in a tissue-specific manner and disrupts ureteric bud branching morphogenesis. |
Targeted gene deletion (>80% coding sequence including PHD domain) in mice, BAT-gal Wnt reporter assay, confocal analysis, microarray expression profiling |
BMC biology |
High |
17425782
|
| 2013 |
Pygo2 acts as a histone methylation reader and context-dependent Wnt/β-catenin coactivator that suppresses luminal/alveolar differentiation of mammary stem/basal cells by binding to the Notch3 locus, recruiting β-catenin, and maintaining a poised/repressed chromatin state at the Notch3 locus; loss of Pygo2 elevates Notch signaling and luminal differentiation markers. |
Epithelia-specific Pygo2 knockout, mammary transplantation, Notch/Wnt pharmacological inhibition/activation, ChIP for β-catenin and chromatin state at Notch3 locus, gene expression profiling |
Cell stem cell |
High |
23684539
|
| 2013 |
Epithelial ablation of Pygo2 in MMTV-Wnt1 mice significantly delays mammary tumor onset and reduces tumor-initiating capability upon transplantation, placing Pygo2 downstream of mammary stem cell accumulation in the transformation step and showing it modulates lineage potential of tumor-initiating cells. |
Epithelia-specific conditional knockout in MMTV-Wnt1 transgenic mice, tumor transplantation assay, lineage analysis |
Oncogene |
High |
23334328
|
| 2014 |
Pygo2 in epithelial cells facilitates β-catenin-induced activation of hair follicle stem/early progenitor cells and trichofolliculoma-like skin hyperplasia; β-catenin and Pygo2 converge to induce accumulation and acetylation of p53 upon cell cycle entry of hair follicle early progenitor cells and in cultured keratinocytes. |
Conditional epithelial Pygo2 knockout, depilation-induced hair regeneration assay, β-catenin gain-of-function mouse model, immunostaining for p53 acetylation, cell culture experiments |
Proceedings of the National Academy of Sciences of the United States of America |
High |
24982158
|
| 2015 |
Pygo2 protein is degraded via the ubiquitin/proteasome pathway through a Cullin 4 (Cul4)-DDB1 E3 ubiquitin ligase complex; Akt-mediated phosphorylation of Pygo2 at serine 48 reduces its ubiquitylation and increases its stability, thus acting downstream of PI3K/Akt and Wnt signaling to stabilize Pygo2. |
Proteasome inhibitor treatment, co-immunoprecipitation of Cul4/DDB1 with Pygo2, site-directed mutagenesis at S48, Akt kinase assays, ubiquitylation assays |
The Journal of biological chemistry |
High |
26170450
|
| 2016 |
Pygo2 activates MDR1 (ABCB1) expression in breast cancer cells via the Wnt/β-catenin pathway; Pygo2 is identified as the most upregulated Wnt pathway component in chemoresistant breast cancer cells, and its inhibition restores drug sensitivity and reduces cancer stem cell populations. |
Wnt pathway-specific PCR array screening, siRNA knockdown, MDR1 reporter assays, cell viability assays, mouse xenograft model |
Oncogene |
Medium |
26876203
|
| 2016 |
Pygo2 is required as a co-activator in the nuclear β-catenin/BCL9/BCL9-2 complex for Wnt target gene transcription (specifically c-Myc); in vivo loss of Pygo2 reduces chemically induced colon tumor development and rescues early tumorigenesis in Ctnnb1 gain-of-function mice, but does not prevent tumor development in Apc loss-of-function mice. |
Pygo2 knockout mice, chemically-induced colon tumor model, conditional intestinal Ctnnb1 GOF and Apc LOF mouse models, target gene expression analysis |
Oncotarget |
High |
27811361
|
| 2016 |
Pygo2 is transiently acetylated by CBP/p300 (but not GCN5/PCAF) at specific lysine residues in its N-terminal homology domain when bound to the active TCF/β-catenin transcription complex; p300-mediated acetylation of Pygo2 at lysines in its nuclear localization sequence displaces Pygo2 from the nucleus to the cytoplasm, consistent with a recycling mechanism post-target gene activation; CBP/p300 presence also increases Pygo2 association with GCN5 independently of Pygo2 acetylation status. |
Co-immunoprecipitation, mutagenesis of lysine residues, subcellular fractionation/localization, Axin2 reporter assays, in vitro acetylation assays |
The Biochemical journal |
High |
27647933
|
| 2018 |
PYGO2, located in the 1q21.3 amplicon, functions as a driver oncogene in prostate cancer; PYGO2 overexpression enhances primary tumor growth and lymph node invasion, PYGO2 depletion inhibits invasion in vitro and tumor progression/metastasis in vivo, and PYGO2 is necessary for transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. |
In vivo gain-of-function tumorigenesis screen, PYGO2 overexpression and shRNA depletion in cell lines and mouse models, patient-derived xenograft models, Wnt reporter assays |
Cancer research |
High |
29769196
|
| 2018 |
Pygo2 inhibition during adipocyte differentiation leads to downregulation of Axin2 in the cytoplasm, releasing Axin2-bound GSK3β to translocate to the nucleus, where it phosphorylates C/EBPβ and Snail, increasing C/EBPβ DNA binding activity and decreasing Snail stability, thereby activating C/EBPα and PPARγ expression and promoting adipogenesis; adipocyte precursor-specific Pygo2 knockout mice show increased adiposity and impaired glucose tolerance. |
Pygo2 conditional knockout mice, primary adipocyte differentiation assays, nuclear/cytoplasmic fractionation, GSK3β nuclear translocation analysis, co-immunoprecipitation, phosphorylation assays, metabolic phenotyping |
Diabetes |
High |
30279163
|
| 2023 |
Pygo2 orchestrates a p53/Sp1/Kit/Ido1 signaling network in prostate cancer cells to create an immune microenvironment hostile to cytotoxic T lymphocytes (CTLs); Pygo2 deletion augments CTL activation and infiltration, sensitizes tumor cells to T cell killing, and enhances efficacy of immune checkpoint blockade, adoptive cell transfer, and MDSC-targeting therapies. |
Transgenic mouse models of metastatic prostate adenocarcinoma, Pygo2 deletion, flow cytometry of CTLs, mechanistic dissection of p53/Sp1/Kit/Ido1 pathway, pharmacological inhibition, immune checkpoint blockade combination experiments |
Science immunology |
High |
36897957
|
| 2023 |
Pygo2 coordinates with H3K4me2/3 modifications to activate BRPF1 transcription by binding to the BRPF1 promoter; Pygo2-driven colon cancer cell proliferation, migration, stemness, and in vivo tumor growth depend on BRPF1 as a downstream effector, and BRPF1 inhibition selectively suppresses Pygo2-high tumor growth. |
Luciferase reporter assay, ChIP-qPCR at BRPF1 promoter, siRNA knockdown, overexpression, in vivo subcutaneous tumor model, GSK5959 pharmacological inhibition |
Experimental cell research |
Medium |
37423512
|
| 2015 |
Pygo2 knockdown in glioma U251 cells inhibits cell proliferation, increases apoptosis, and reduces glioma cancer stem-like cell sphere number and size, linked mechanistically to decreased H3K4me3 levels, establishing Pygo2's role in histone H3K4 trimethylation as a driver of glioma cell survival. |
Lentiviral siRNA knockdown, cell proliferation assay, apoptosis assay, neurosphere assay, H3K4me3 immunostaining/western blot |
Journal of molecular neuroscience |
Medium |
25869613
|
| 2022 |
EFNA4 (Ephrin A4) physically interacts with PYGO2 and positively regulates PYGO2 protein expression; EFNA4 knockdown blocks Wnt/β-catenin signaling in HCC cells in a PYGO2-dependent manner, as PYGO2 overexpression rescues the signaling and tumor phenotypes caused by EFNA4 loss. |
Co-immunoprecipitation (EFNA4-PYGO2 interaction), siRNA knockdown, overexpression rescue experiments, Wnt/β-catenin pathway readouts, cell proliferation/invasion/angiogenesis assays |
Cancer biology & therapy |
Medium |
36404439
|
| 2021 |
Pygo2 directly binds to the MDR1 promoter region and promotes MDR1 transcriptional activation in gastric cancer; Pygo2 knockdown in drug-resistant gastric cancer cells downregulates MDR1 and restores sensitivity to cisplatin. |
ChIP/promoter binding assay for Pygo2 at MDR1 promoter, siRNA knockdown, MDR1 expression analysis, drug sensitivity assay |
Journal of Cancer |
Medium |
33854595
|