| 1999 |
Kaiso was identified as a novel BTB/POZ zinc finger transcription factor that directly interacts with p120-catenin (p120ctn). Yeast two-hybrid screening identified Kaiso as a p120ctn-binding partner; the interaction was confirmed by co-immunoprecipitation with p120ctn-specific antibodies. Mapping studies showed the interaction involves Arm repeats 1-7 of p120ctn and the C-terminal 200 amino acids of Kaiso. Kaiso homodimerizes via its POZ domain but does not heterodimerize with BCL-6. Kaiso localizes to the nucleus and nuclear dots. |
Yeast two-hybrid screen, co-immunoprecipitation, immunolocalization, domain mapping |
Molecular and cellular biology |
High |
10207085
|
| 2001 |
Kaiso is a methylation-dependent transcriptional repressor that requires at least two symmetrically methylated CpG dinucleotides (preferably within 5'CGCG) for DNA binding. Kaiso is a constituent of one of two methyl-CpG binding complexes originally designated as MeCP1. The zinc finger motifs are responsible for DNA binding. Kaiso behaves as a methylation-dependent transcriptional repressor in transient transfection assays. |
Biochemical purification, transient transfection reporter assays, complex fractionation (MeCP1) |
Genes & development |
High |
11445535
|
| 2002 |
Kaiso is a dual-specificity DNA-binding protein that recognizes both a sequence-specific consensus (TCCTGCNA, minimal core CTGCNA) and methylated CpG dinucleotides via its zinc fingers. Zinc fingers 2 and 3 are necessary and sufficient for sequence-specific DNA binding. p120ctn inhibits Kaiso DNA binding at both recognition sites. Kaiso has higher affinity for the TCCTGCNA consensus than for methylated CpG sites. |
EMSA with GST-Kaiso fusion proteins, domain deletion analysis, SELEX-type binding assays |
Nucleic acids research |
High |
12087177
|
| 2003 |
Kaiso is a component of the human N-CoR corepressor complex. The Kaiso/N-CoR complex binds specific CpG-rich sequences in a methylation-dependent manner in vitro. In vivo, Kaiso recruits the N-CoR complex to the MTA2 gene promoter in a methylation-dependent manner, resulting in histone hypoacetylation and H3 lysine 9 methylation at the MTA2 locus. Kaiso is required for transcriptional repression of the methylated MTA2 locus, and this repression requires a functional N-CoR deacetylase complex. |
Co-immunoprecipitation, in vitro binding assays, chromatin immunoprecipitation (ChIP), reporter assays, RNAi depletion |
Molecular cell |
High |
14527417
|
| 2004 |
Kaiso is required to maintain transcriptional silencing during early Xenopus laevis development. xKaiso depletion causes premature zygotic gene expression before the mid-blastula transition (MBT), phenocopying hypomethylated embryos. Wild-type human Kaiso mRNA rescues the xKaiso depletion phenotype, establishing functional conservation. xKaiso acts as a global repressor of methylated genes. |
Morpholino antisense depletion in Xenopus, mRNA rescue, gene expression profiling |
Development (Cambridge, England) |
High |
15548582
|
| 2004 |
Kaiso contains a functional nuclear localization signal (NLS) that mediates interaction with importin-alpha2 for nuclear import. Mutation of a key lysine in the NLS significantly inhibits nuclear localization. Wild-type but not NLS-defective Kaiso interacts with importin-alpha2 both in vitro and in vivo. The NLS is required for Kaiso-mediated transcriptional repression. |
NLS identification, beta-gal/GFP fusion reporter localization, Co-IP with importin-alpha2, minimal promoter reporter assays, site-directed mutagenesis |
Journal of cell science |
High |
15564377
|
| 2004 |
Nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression. An NLS in p120ctn was identified; mutation of key lysines in the NLS inhibited p120ctn nuclear localization. Using minimal promoter assays, p120ctn's regulatory effect on Kaiso transcriptional activity requires nuclear translocation of p120ctn, not cytoplasmic sequestration of Kaiso. |
NLS mutagenesis, heterologous reporter (beta-gal/GFP), minimal promoter reporter assays, nuclear fractionation |
Journal of cell science |
High |
15138284
|
| 2004 |
Kaiso represses the non-canonical Wnt ligand xWnt11 in Xenopus, and xWnt11 is a direct gene target of xKaiso. p120-catenin association relieves xKaiso repression of xWnt11 in vivo. xKaiso knockdown results in increased xWnt11 expression contributing to gastrulation defects. |
Morpholino depletion, mRNA rescue, dominant-negative Wnt11, reporter assays in Xenopus |
Nature cell biology |
High |
15543138
|
| 2004 |
Rapsyn gene is a direct sequence-specific transcriptional target of Kaiso. Kaiso associates with the rapsyn promoter in vivo (ChIP). Delta-catenin (a brain-specific p120 subfamily member) forms a complex with Kaiso. In C2C12 myocytes, Kaiso and delta-catenin activate the rapsyn promoter in a muscle-specific manner. |
Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, minimal promoter reporter assays |
Molecular and cellular biology |
High |
15282317
|
| 2005 |
Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, c-Myc) in Xenopus in conjunction with TCF/LEF. Kaiso and TCF coassociate. p120-catenin relieves Kaiso-mediated repression of Siamois. Kaiso suppresses beta-catenin-induced axis duplication and TCF-3 rescues Kaiso depletion phenotypes, establishing functional interdependency between Kaiso/p120ctn and beta-catenin/TCF pathways. |
Xenopus embryo microinjection, co-immunoprecipitation (Kaiso-TCF), beta-catenin ChIP on Siamois promoter, reporter assays, epistasis experiments |
Developmental cell |
High |
15935774
|
| 2005 |
Kaiso associates with the matrilysin promoter in vivo via the Kaiso binding site (KBS). Kaiso specifically represses transcription of the matrilysin promoter; mutation of KBS or siRNA depletion of Kaiso abrogates this repression. Kaiso blocks beta-catenin-mediated activation of matrilysin. p120ctn overexpression inhibits Kaiso-DNA binding and repression, but only when p120ctn can translocate to the nucleus (NLS-dependent). |
Chromatin immunoprecipitation (ChIP), minimal promoter reporter assays, KBS mutagenesis, siRNA depletion, p120ctn nuclear localization mutant |
Experimental cell research |
High |
15817151
|
| 2005 |
CTCF (enhancer blocker) interacts with Kaiso as a binding partner. The interaction occurs through the C-terminal region of CTCF and the POZ domain of Kaiso. CTCF was specifically co-immunoprecipitated by Kaiso monoclonal antibodies from nuclear lysates. A Kaiso binding site near the CTCF binding site in the 5' beta-globin insulator reduces the enhancer-blocking activity of CTCF. |
Yeast two-hybrid, co-immunoprecipitation from nuclear lysates, insulation assay |
The Journal of biological chemistry |
Medium |
16230345
|
| 2006 |
Kaiso-null mice are viable and fertile with no detectable developmental abnormalities, but display delayed onset of intestinal tumorigenesis when crossed with Apc(Min/+) mice. Kaiso is upregulated in murine intestinal tumors and expressed in human colon cancers, indicating a role in intestinal cancer promotion. |
Gene knockout mouse, Apc(Min/+) cross, tumor quantification, immunohistochemistry |
Molecular and cellular biology |
High |
16354691
|
| 2006 |
Frodo mediates stabilization of p120-catenin in response to Wnt signals, which in turn promotes Kaiso nuclear sequestration or removal. p120-catenin binds Frodo, and Frodo interacts with Dishevelled (Dsh). Wnt signals thus act through Dsh-Frodo-p120ctn to regulate the p120ctn/Kaiso signaling pathway. |
Co-immunoprecipitation, Xenopus embryo epistasis, protein stability assays |
Developmental cell |
Medium |
17084360
|
| 2008 |
Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer. Kaiso binds the CDKN2A promoter in a methylation-dependent manner. Kaiso depletion induces tumor suppressor gene expression without affecting DNA methylation levels, sensitizing colon cancer cells to cell cycle arrest and cell death. |
ChIP, siRNA depletion, RT-PCR, cell cycle and apoptosis assays |
Cancer research |
High |
18794111
|
| 2008 |
H. pylori cag(+) strains induce translocation of p120-catenin to the nucleus, which relieves Kaiso-mediated transcriptional repression of mmp-7 (matrix metalloproteinase-7). This mechanism is cag- and p120-dependent and results in increased MMP-7 mRNA and protein levels. |
siRNA knockdown, nuclear fractionation, ex vivo gastric gland culture, RT-PCR |
Molecular biology of the cell |
Medium |
18653469
|
| 2009 |
The non-methylated DNA-binding function of Kaiso (CTGCNA) is not evolutionarily conserved in frogs, fish, or chicken. In Xenopus, phenotypic abnormalities of xKaiso depletion are independent of the CTGCNA-dependent DNA-binding function. xKaiso does not regulate xWnt11 or Siamois; instead, the major phenotypic defects are premature transcription activation and activation of a p53-dependent cell-death pathway. |
Comparative species analysis of Kaiso DNA-binding, morpholino depletion, reporter assays, mutant Kaiso rescue experiments |
Development (Cambridge, England) |
Medium |
19158185
|
| 2010 |
Kaiso interacts with the POZ-ZF protein Znf131 via POZ-POZ domain interaction. GST pull-down and co-immunoprecipitation confirmed the Kaiso-Znf131 in vivo interaction. Znf131 is a transcriptional activator (activates artificial promoter containing ZBE). Kaiso overexpression significantly inhibits Znf131-mediated transcriptional activation, and co-expression of p120ctn relieves this Kaiso inhibition. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, EMSA, CAST (SELEX), reporter assay |
Experimental cell research |
High |
20303951
|
| 2010 |
Kaiso localizes at the mitotic spindle and is a constituent of the pericentriolar material (PCM), belonging to a pericentrin molecular complex. During interphase, Kaiso is on microtubular structures and centrosomes; at metaphase, on centrosomes and spindle microtubules; during telophase, at the midbody. Two domains mediate spindle/centrosome targeting: SA1 (spindle-associated domain 1, center of protein) and SA2 (just before zinc fingers). Overexpression of full-length Kaiso causes mitotic cell arrest and cell death; Kaiso knockdown accelerates cell proliferation. |
GFP-tagged fragment localization, immunofluorescence throughout cell cycle, domain deletion analysis, Kaiso knockdown/overexpression with proliferation readout |
PloS one |
Medium |
20169156
|
| 2011 |
Wnt3a-induced phosphorylation of p120-catenin at Ser268 and Ser269 (by CK1ε) enhances its binding to Kaiso, preventing Kaiso-mediated inhibition of the β-catenin-Tcf-4 complex. Kaiso associates with both Tcf-4 and β-catenin. p120-catenin disrupts Tcf-4-Kaiso and β-catenin-Kaiso interactions, freeing Tcf-4 and β-catenin to form their complex and enabling Kaiso to bind methylated CpG islands (e.g., CDKN2A promoter). |
Co-immunoprecipitation, phospho-site mutagenesis, reporter assays, ChIP, siRNA knockdown |
Journal of cell science |
Medium |
21670201
|
| 2012 |
Crystal structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated KBS DNA and with symmetrically methylated E-cadherin promoter-derived DNA were solved. Recognition of specific bases in the major groove of KBS and mCpG sites is mediated by residues in zinc fingers 1 and 2 through classical and methyl CH···O hydrogen-bonding interactions. The C-terminal extension following zinc finger 3 binds in the opposing minor groove and is required for high-affinity binding; this region is disordered in free protein and folds upon DNA binding. |
X-ray crystallography, structural analysis of protein-DNA complexes |
Proceedings of the National Academy of Sciences of the United States of America |
High |
22949637
|
| 2012 |
Kaiso requires all three zinc fingers plus adjacent protein regions (N-terminal extension for stability and extended C-terminal region for augmented binding) for high-affinity DNA recognition of both methylated and sequence-specific sites. Contrary to prior findings, zinc fingers 2 and 3 alone are not sufficient for high-affinity binding. |
Systematic domain deletion/mutagenesis, in vitro binding assays (EMSA, ITC) |
FEBS letters |
High |
22300642
|
| 2012 |
Kaiso associates with and represses the cyclin D1 promoter via both the KBS consensus site and methylated CpG dinucleotides. The methyl-CpG sites are critical for Kaiso binding to the cyclin D1 promoter, while the KBS stabilizes binding. Kaiso repressed the minimal cyclin D1 promoter-reporter in a dose-dependent, KBS-specific, and methyl-CpG-dependent manner. |
EMSA, ChIP, minimal promoter reporter assay, KBS mutagenesis |
PloS one |
High |
23226276
|
| 2012 |
Kaiso interacts with the transcriptional corepressor MTG16. This interaction is mediated by Kaiso's zinc finger domains. MTG16 family members are required for efficient repression of a reporter construct containing Kaiso binding sites and the known Kaiso target MMP-7/matrilysin. ChIP places MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. MTG16's contribution to repression requires Kaiso binding to its DNA binding site. |
Yeast two-hybrid, co-immunoprecipitation, reporter assay, chromatin immunoprecipitation |
PloS one |
High |
23251453
|
| 2012 |
In vivo, ZBTB33/Kaiso binds to unmethylated regions of the genome associated with actively expressed genes and highly acetylated histones, rather than methylated DNA as predicted. DNA methylation and nucleosome occupancy restrict Kaiso access to potential binding sites. |
ChIP-seq for Kaiso, genome-wide DNA methylation analysis, bioinformatic integration |
Epigenetics & chromatin |
Medium |
23693142
|
| 2012 |
SMRT corepressor is tethered to promoter-proximal regions in preadipocytes primarily via KAISO through the conserved TCTCGCGAGA motif. KAISO, similar to SMRT, functions as an adipogenic repressor that modulates the mitotic clonal expansion phase of adipogenesis; KAISO knockdown increases fat accumulation and accelerates cell cycle. |
Genome-wide ChIP-seq for SMRT and KAISO, ChIP-seq motif analysis, siRNA knockdown with adipogenesis assay |
Molecular cell |
Medium |
22521691
|
| 2012 |
Dyrk1A kinase is a component of the p120-catenin-Kaiso trajectory of the Wnt pathway. Dyrk1A positively modulates p120-catenin protein levels, impacting p120-catenin and Kaiso gene targets (siamois, wnt11). A consensus Dyrk phosphorylation site in p120-catenin was identified; a phosphomimetic mutant of p120-catenin shows enhanced capacity to promote Wnt-11 and Siamois expression. |
Xenopus epistasis/rescue, mammalian cell experiments, phosphomimetic mutagenesis, Dyrk1A Co-IP/overexpression |
Journal of cell science |
Medium |
22389395
|
| 2014 |
KAISO is induced by DNA damage in p53-expressing cells and interacts with the p53-p300 complex. KAISO increases acetylation of p53 at K320 and K382 residues while decreasing K381 acetylation. This specific p53 acetylation pattern increases p53 DNA binding and potently induces CDKN1A and apoptotic gene transcription. In Kaiso-KO mouse embryonic fibroblasts, p53-promoter binding and upregulation of p21 and apoptosis genes are significantly compromised. |
Co-immunoprecipitation (KAISO-p53-p300), p53 acetylation assays, ChIP, KO mouse fibroblasts, reporter assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
25288747
|
| 2015 |
Nuclear p120-catenin relieves Kaiso-mediated transcriptional repression of Wnt11 in anchorage-independent ILC cells. Wnt11 upregulation in anchorage-independent conditions is controlled by nuclear p120 through inhibition of Kaiso repression. Wnt11 promotes RhoA activation causing ILC anoikis resistance. |
mRNA profiling, nuclear p120 fractionation, siRNA knockdown of Kaiso/Wnt11, RhoA activity assay, anoikis assay |
Disease models & mechanisms |
Medium |
25713299
|
| 2016 |
ZBTB33/Kaiso mediates cell-specific cell cycle regulation through direct occupancy of cyclin D1 and cyclin E1 promoters. In HeLa cells, ZBTB33 occupies and activates cyclin D1 and E1 promoters, promoting RB phosphorylation and E2F transcriptional activity to accelerate G1-to-S transition. In HEK293 cells, ZBTB33 indirectly reduces cyclin E abundance, decreasing RB phosphorylation and decelerating G1 transition. |
ZBTB33 depletion/overexpression, ChIP, cell cycle analysis (flow cytometry), RB phosphorylation assays, E2F reporter assay |
The Journal of biological chemistry |
Medium |
27694442
|
| 2018 |
Glutamate 535 (E535) in Kaiso zinc finger 1 is critical for preferential recognition of methylated CpG (mCpG) over unmethylated CpG, with a ~100-fold difference in affinity. E535 forms multiple direct contacts with mCpG including CH···O hydrogen bonds. NMR and X-ray crystallography with E535 mutants provided first direct experimental evidence for CH···O hydrogen bond formation between Kaiso and 5-methylcytosine. |
X-ray crystallography, NMR spectroscopy, in vitro protein-DNA binding assays, site-directed mutagenesis of E535 |
Biochemistry |
High |
29546986
|
| 2018 |
Kaiso is SUMOylated at lysine 42 (K42) as a monoSUMOylation under normal physiological conditions in kidney-origin cell lines. SUMOylated Kaiso activates transcription from exogenous methylated promoters, while deSUMOylated Kaiso retains transcriptional repressor activity. Hyperosmotic stress rapidly and reversibly triggers deSUMOylation of Kaiso. Genomic K42R editing (deSUMOylated Kaiso) led to misregulation of ion transport and immune response genes; TRIM25 is a direct transcriptional target of Kaiso. |
SUMO site mutagenesis (K42R), CRISPR/Cas9 genome editing, reporter assays with methylated promoters, hyperosmotic stress treatment, KO mouse model (salt diet) |
Cell death and differentiation |
High |
29472715
|
| 2018 |
Kaiso binds to methylated regions of the miR-200c promoter in a methylation-dependent manner (confirmed by ChIP), repressing miR-200c expression. EGFR signaling regulates Kaiso-mediated silencing of miR-200c. miR-200c and Kaiso regulate each other in a feedback loop, with miR-200c overexpression decreasing Kaiso, ZEB1, and EGFR. |
ChIP assay for Kaiso-miR-200c promoter binding, 5-aza treatment, siRNA knockdown, miR-200c overexpression |
Cancer letters |
Medium |
29751044
|
| 2020 |
A conformational switch in Kaiso's E535 residue enables differential readout of methylated (mCpG) and sequence-specific (KBS) DNA. With methylated DNA, multiple direct contacts between E535 and the 5' mCpG site dominate binding, tolerating different flanking sequences. With KBS, E535 acts as an indirect screen for 5' flanking sequence, with tyrosine-DNA interactions stabilizing optimal DNA conformation. Intrinsic variations in DNA flexibility contribute to differential specificity. |
X-ray crystallography, targeted mutagenesis, in vitro DNA binding assays, nucleotide substitutions |
Biochemistry |
High |
32352758
|
| 2021 |
Kaiso deficiency in human renal cancer cells leads to whole-genome hypermethylation at genic regions, enhancers, and regions with low histone modifications, while protecting these regions from demethylation. Kaiso immunoprecipitates with de novo DNA methyltransferases DNMT3a/3b but not with maintenance methyltransferase DNMT1, suggesting Kaiso modulates genome methylation by attracting de novo methyltransferases. |
CRISPR/Cas9-generated Kaiso-knockout cells, whole-genome methylation analysis, co-immunoprecipitation of Kaiso with DNMT3a/3b |
International journal of molecular sciences |
Medium |
34299205
|
| 2021 |
ZBTB33 mutations in clonal hematopoiesis and MDS confer a competitive advantage to hematopoietic stem cells in vivo. Zbtb33-edited mouse HSPCs show increased genome-wide intron retention, suggesting ZBTB33 mutations potentially link DNA methylation reading and RNA splicing. |
CRISPR editing of Zbtb33 in mouse HSPCs, competitive transplantation assay, RNA-seq for intron retention |
Blood cancer discovery |
Medium |
34568833
|
| 2022 |
TRIM28 enhances SUMOylation of Kaiso, leading to decreased methyl-dependent transcriptional repression. The RBCC domain of TRIM28 interacts with the BTB/POZ domain and zinc fingers of Kaiso; the PHD-bromodomain of TRIM28 is sufficient for interaction with Kaiso zinc fingers. Kaiso also enhances SUMOylation of TRIM28, suggesting mutual self-enhancement of SUMOylation. |
Co-immunoprecipitation, domain deletion mapping, SUMOylation assays, reporter assays |
Biochimie |
Medium |
36252888
|
| 2022 |
Conserved proline P588 (in the C-terminal linker between zinc finger 3 and the DNA-binding extension) is required for efficient Kaiso-DNA binding. Substitution of P588 to alanine negatively affects DNA binding; molecular dynamics simulations show allosteric effects on the entire zinc finger domain. The cis-conformation of P588 is important for DNA-binding affinity. |
Site-directed mutagenesis, in vitro DNA binding assays, molecular dynamics simulation |
International journal of molecular sciences |
Medium |
36555132
|
| 2024 |
In vivo ChIP-seq in Caki-1 renal carcinoma cells (using Kaiso-deficient cells as negative control) revealed that the principal binding motifs for Kaiso are CGCG and CTGCNAT, with 60% of binding sites containing both sequences. Kaiso is present at CpG islands with a preference for methylated ones. An E535A mutant (unable to bind methylated DNA in vitro) can still bind CTGCNA sequences in vivo, confirming the dual-binding mode in cells. |
ChIP-seq with Kaiso-KO cells as negative control, E535A mutant ChIP-seq, bisulfite sequencing, gene expression analysis |
Epigenetics & chromatin |
High |
39702290
|
| 2016 |
RhoH forms a multi-protein complex with Kaiso and p120-catenin that co-localizes at chemokine-induced actin-containing cell protrusion sites in Jurkat T cells. RhoH knockdown disrupts Kaiso localization to protrusion sites and to the nucleus after chemokine stimulation. Kaiso downregulation alters cell migration and actin polymerization in chemokine-stimulated T cells. |
In vivo biotinylation/mass spectrometry, co-immunoprecipitation, immunofluorescence, RhoH knockdown, migration/actin assays |
Small GTPases |
Medium |
27574848
|
| 2015 |
Kaiso directly binds to the E-cadherin promoter in a methylation-dependent manner (confirmed by ChIP in PC-3 cells). Kaiso inhibition results in increased E-cadherin expression, re-establishment of cell-cell contacts, and reversal of mesenchymal markers N-cadherin and fibronectin in prostate cancer cells. EGF receptor signaling causes nuclear localization of Kaiso. |
ChIP for Kaiso at E-cadherin promoter, shRNA knockdown, immunofluorescence, Western blot |
The American journal of pathology |
Medium |
22974583
|
| 2015 |
KAISO directly binds and transcriptionally activates APAF1 only in cells expressing WT p53, by augmenting p53 binding to the APAF1 promoter distal p53RE#1. A nearby NF-κB response element mediates APAF1 repression; ectopic RelA/p65 sequesters KAISO in the cytoplasm, preventing nuclear KAISO-p53 interaction and thus blocking APAF1 activation. |
Reporter assays, ChIP, co-immunoprecipitation, ectopic p65 expression with cytoplasmic fractionation |
Biochimica et biophysica acta |
Medium |
26183023
|
| 2016 |
Kaiso binds directly to the miR-31 promoter in a methylation-dependent manner (ChIP). Kaiso represses miR-31 expression, promoting prostate cancer cell migration and invasiveness. miR-31 overexpression decreases these malignant phenotypes, while anti-miR-31 restores them in Kaiso-depleted cells. |
ChIP, miRNA array, siRNA/shRNA depletion, cell migration/invasion assays |
Oncotarget |
Medium |
26734997
|
| 2013 |
Kaiso overexpression in intestinal-specific transgenic mice (driven by villin promoter) causes crypt expansion, increased differentiation into secretory cell lineages (goblet, Paneth, enteroendocrine cells), reduced proliferation, and decreased Notch signaling target HES-1. p120ctn is recruited to the nucleus in transgenic mice intestinal cells, suggesting Kaiso antagonizes p120ctn's anti-inflammatory function. |
Transgenic mouse model with intestinal-specific Kaiso overexpression, histology, immunohistochemistry, immunofluorescence |
PloS one |
Medium |
24040197
|
| 2017 |
Kaiso directly associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon cancer cells (ChIP). In Kaiso transgenic mice, Notch1 and Dll-1 expression are reduced while Jagged-1 is increased. Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation, acting through differential regulation of Notch ligands. |
ChIP in three colon cancer cell lines, transgenic mouse intestine analysis, real-time PCR, immunohistochemistry |
Cell communication and signaling |
Medium |
28637464
|
| 2019 |
p53 transcriptionally activates KAISO/ZBTB33 by binding to p53RE1 (5'-upstream, -4326 to -4227) and p53RE3 (exon 2, +2929 to +2959). ATM/ATR kinase-mediated p53 phosphorylation at Ser-15 or Ser-37 activates KAISO transcription during early DNA damage response (DDR). Acetylated p53 activates KAISO transcription at p53RE1 during later DDR phase. |
Reporter assays with various p53RE constructs, ChIP, oligonucleotide pulldown, phospho-specific mutants |
The Journal of biological chemistry |
Medium |
31296660
|
| 2016 |
Kaiso directly binds to the methylated THBS1 promoter and represses its expression. Kaiso depletion results in decreased expression of CD47 and its ligand SIRPA, promoting macrophage polarization towards M1 phenotype. Kaiso-depleted xenograft tissues showed higher phagocytosis and increased M1 macrophage infiltration. |
ChIP for Kaiso at THBS1 promoter, siRNA depletion, in vivo xenograft with immunohistochemistry |
Cancers |
Medium |
37190208
|
| 2016 |
Kaiso binds unmethylated KBS in the human ICR1 (imprinting control region of H19/IGF2), and Kaiso depletion or CRISPR/Cas9 deletion of the ICR1-KBS results in reduced methylation of the paternal ICR1. Kaiso also affects transcription of the lncRNA H19 via ICR1. |
ChIP, EMSA, lentiviral Kaiso knockdown, CRISPR/Cas9 editing of KBS, bisulfite sequencing |
Clinical epigenetics |
Medium |
27152123
|
| 2021 |
Kaiso regulates osteoblast differentiation and mineralization through the Itga10/PI3K/AKT signaling pathway. Itga10 (integrin subunit α10) is identified as a direct transcriptional target of Kaiso by ChIP and luciferase reporter assays. Kaiso is downregulated during osteoblast differentiation; gain- and loss-of-function modulate osteoblast differentiation in vitro and in vivo. |
ChIP, luciferase reporter assays, gain/loss-of-function in MC3T3-E1 cells, in vivo mouse experiments, pathway analysis |
International journal of molecular medicine |
Medium |
33576467
|
| 2021 |
Kaiso protects human endothelial cells against apoptosis by differentially regulating BCL2 family member expression: Kaiso overexpression increases BCL2 and reduces BAX and BIK expression through differential regulation of gene promoter activity. Both methylated DNA and KBS-dependent mechanisms contribute to Kaiso's gene regulatory activity in endothelial cells. p120ctn cooperates with Kaiso in this transcriptional regulation. |
Kaiso overexpression/knockdown, cell viability assay, promoter reporter assay, Western blot, co-immunoprecipitation |
Scientific reports |
Medium |
28769046
|
| 2013 |
Kaiso is a key regulator of spleen germinal center formation. Kaiso represses Bcl6 expression (confirmed by ChIP and transcription assays). In Kaiso-KO mice, derepressed Bcl6 increases cell proliferation by suppressing p27, p21, and Gadd45a while upregulating c-Myc. |
ChIP, reporter assays, KO mouse analysis, immunohistochemistry, B lymphocyte ectopic expression |
Biochemical and biophysical research communications |
Medium |
24269670
|