Alternative titles; symbols
HGNC Approved Gene Symbol: ZBTB33
Cytogenetic location: Xq24 Genomic coordinates (GRCh38): X:120,250,812-120,258,398 (from NCBI)
KAISO is a transcriptional regulator that binds, via its zinc fingers, to DNA sequences containing methylated CGCG or to the consensus KAISO-binding site (KBS) TCCTGCNA (Filion et al., 2006).
Armadillo-repeat proteins (e.g., CTNNB1; 116806) are often involved in protein-protein interactions, notably with cadherins (e.g., CDH1; 192090) and APC (611731), in different subcellular locations. Using a yeast 2-hybrid screen of a murine liver cDNA library with the armadillo-repeat protein p120 (CTNND1; 601045) as bait, followed by screening murine lung and spleen cDNA libraries and searching human EST databases, Daniel and Reynolds (1999) obtained mouse and human cDNAs encoding KAISO. ('Kaiso' is Caribbean slang for calypso music, which accompanied the late-night cloning of this gene (Daniel, 2001).) The deduced 672-amino acid human protein is 87% identical to the mouse protein, with mostly conservative changes, and has a calculated molecular mass of 80 kD. KAISO contains an N-terminal POZ/BTB domain and 3 C-terminal zinc finger motifs. Northern blot analysis of mouse tissues revealed ubiquitous expression of 5- to 6-kb transcripts. Western blot analysis showed that KAISO migrated as a 95-kD doublet in most mammalian cell lines examined, including human cells. In rodent cell lines, Kaiso migrated as a 110-kD doublet. Immunofluorescence analysis demonstrated nuclear localization of endogenous Kaiso in canine and mouse cells.
Using immunoprecipitation analysis, Daniel and Reynolds (1999) showed that KAISO interacted with CTNND1, but not with CTNNB1, CTNNA1 (116805), or CDH1, in canine and human cells. Yeast 2-hybrid analysis indicated that the armadillo repeats of mouse Ctnnd1 interacted with a region flanking the zinc finger domain of mouse Kaiso.
Prokhortchouk et al. (2001) found that, in a human erythroleukemia cell line and in mouse liver, KAISO associated with a 700-kD methyl-CpG-binding complex that was distinct from the MBD2 (603547)-containing methyl-CpG-binding complex. Using mouse and human cells and constructs, they showed that the zinc finger domain of KAISO bound methyl-CpG and that KAISO mediated binding of the methyl-CpG-binding complex to the core sequence MGMG, where M is 5-methylcytosine. KAISO repressed transcription of a methylated reporter gene, and repression required both the POZ and zinc finger domains of KAISO. Prokhortchouk et al. (2001) concluded that KAISO is a methylation-dependent transcriptional repressor.
Daniel et al. (2002) found that mouse Kaiso functioned as a dual-specificity DNA-binding protein that recognized the consensus sequence TCCTGCNA as well as methyl-CpG dinucleotides. Kaiso zinc fingers 2 and 3 were necessary and sufficient for sequence-specific DNA binding, and the methyl-CpG-dependent DNA-binding activity of Kaiso was distinct from its sequence-specific DNA binding. Kaiso had a higher affinity for the TCCTGCNA consensus than for methyl-CpG sites, and binding of Kaiso to either site was inhibited by Ctnnd1.
Rodova et al. (2004) found that Ctnnd2 (604275) formed a complex with Kaiso, and that both proteins localized to nuclei of C2C12 mouse myocytes and to the postsynaptic domain of the mouse neuromuscular junction. Chromatin immunoprecipitation analysis of C2C12 cells showed that endogenous Kaiso coprecipitated with the Rapsyn (RAPSN; 601592) promoter. Minimal promoter assays demonstrated that mouse Kaiso and Ctnnd2 activated the mouse and human RAPSYN promoter, and a human cell line lacking Ctnnd2 expression showed no Kaiso-mediated RAPSYN activation. Site-specific mutation of the RAPSYN promoter to produce the -38A-G (601592.0006) mutation that causes postsynaptic congenital myasthenic syndrome (CMS; 608931) resulted in reduced Kaiso-mediated activation of the RAPSYN promoter. Rodova et al. (2004) concluded that KAISO, CTNND2, and myogenic transcription factors regulate synapse-specific transcription of RAPSYN.
Using a gel retardation assay, Filion et al. (2006) found that the isolated zinc finger domains of KAISO and the related proteins ZBTB4 (612308) and ZBTB38 (612218) bound methylated DNA, and that all 3 proteins repressed the expression of a methylated reporter gene.
Using quantitative RT-PCR, Lopes et al. (2008) found that KAISO depletion via small interfering RNA induced expression of tumor suppressor genes MGMT (156569), HIC1 (603825), and CDKN2A (600160) without affecting DNA methylation levels in human colon cancer cell lines. As a consequence, colon cancer cells became susceptible to cell cycle arrest and cell death mediated by chemotherapy. Chromatin immunoprecipitation analysis showed that KAISO bound a methylated CpG island containing KAISO-binding sites in the promoter region of the CDKN2A gene. Lopes et al. (2008) concluded that KAISO is a methylation-dependent 'opportunistic' oncogene that silences tumor suppressor genes when they become hypermethylated.
By genomic sequence analysis, Daniel and Reynolds (1999) mapped the human KAISO gene to Xq23. They mapped the mouse Kaiso gene to the X chromosome also.
Daniel, J. M. Personal Communication. Baltimore, Md. 4/12/2001.
Daniel, J. M., Reynolds, A. B. The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Molec. Cell. Biol. 19: 3614-3623, 1999. [PubMed: 10207085] [Full Text: https://doi.org/10.1128/MCB.19.5.3614]
Daniel, J. M., Spring, C. M., Crawford, H. C., Reynolds, A. B., Baig, A. The p120(ctn)-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides. Nucleic Acids Res. 30: 2911-2919, 2002. [PubMed: 12087177] [Full Text: https://doi.org/10.1093/nar/gkf398]
Filion, G. J. P., Zhenilo, S., Salozhin, S., Yamada, D., Prokhortchouk, E., Defossez, P.-A. A family of human zinc finger proteins that bind methylated DNA and repress transcription. Molec. Cell. Biol. 26: 169-181, 2006. [PubMed: 16354688] [Full Text: https://doi.org/10.1128/MCB.26.1.169-181.2006]
Lopes, E. C., Valls, E., Figueroa, M. E., Mazur, A., Meng, F.-G., Chiosis, G., Laird, P. W., Schreiber-Agus, N., Greally, J. M., Prokhortchouk, E., Melnick, A. Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. Cancer Res. 68: 7258-7263, 2008. [PubMed: 18794111] [Full Text: https://doi.org/10.1158/0008-5472.CAN-08-0344]
Prokhortchouk, A., Hendrich, B., Jorgensen, H., Ruzov, A., Wilm, M., Georgiev, G., Bird, A., Prokhortchouk, E. The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev. 15: 1613-1618, 2001. [PubMed: 11445535] [Full Text: https://doi.org/10.1101/gad.198501]
Rodova, M., Kelly, K. F., VanSaun, M., Daniel, J. M., Werle, M. J. Regulation of the rapsyn promoter by Kaiso and delta-catenin. Molec. Cell. Biol. 24: 7188-7196, 2004. [PubMed: 15282317] [Full Text: https://doi.org/10.1128/MCB.24.16.7188-7196.2004]