Disease relevance of ZBTB33

• Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome [1].
• Kaiso belongs to the zinc finger and broad-complex, tramtrack and bric-a-brac/poxvirus and zinc finger (BTB/POZ) protein family that has been implicated in tumorigenesis [2].

Psychiatry related information on ZBTB33

• To investigate the potential association of Kaiso disfunction with pathogenesis of Rett syndrome, we approached the analysis at two different levels [3].

High impact information on ZBTB33

• As Kaiso associates with p120 catenin, Kaiso may link events at the cell surface with DNA methylation-dependent gene silencing [4].
• We find that Kaiso behaves as a methylation-dependent transcriptional repressor in transient transfection assays [4].
• In vitro, the Kaiso/N-CoR complex binds specific CpG-rich sequences in a methylation-dependent manner [5].
• Kaiso, a structurally unrelated protein, has also been shown to bind methylated CGCGs through its three Krüppel-like C2H2 zinc fingers [6].
• The human genome contains two uncharacterized proteins, ZBTB4 and ZBTB38, that contain Kaiso-like zinc fingers [6].

Chemical compound and disease context of ZBTB33

• The X-linked methyl binding protein gene Kaiso is highly expressed in brain but is not mutated in Rett syndrome patients [3].

Biological context of ZBTB33

• CTCF DNA binding is methylation sensitive, and the methylated Rb-CTCF site is recognized by the Kaiso methyl-CpG-binding protein [7].
• This is the first evidence suggesting that CTCF protects the Rb gene promoter, a classic CpG island, against DNA methylation, and when such control region is abnormally methylated Kaiso, and probably its associated repressor complex, induce epigenetic silencing of the promoter [7].
• Further analysis ascertained that this CpG is contained in a sequence characterized by putative binding sites for the AP2, Sp1 and KAISO factors [8].
• One of the major goals in this study was to assess the differential gene expression of p120(ctn), Kaiso, and VE-cadherin in HCAEC at specific locations along the wound border to further our understanding of the molecular mechanisms involved in wound closure [9].
• A key component of the activity is Kaiso, a protein with POZ and zinc-finger domains that is known to associate with p120 catenin [4].

Anatomical context of ZBTB33

• Laminar shear stress differentially modulates gene expression of p120 catenin, Kaiso transcription factor, and vascular endothelial cadherin in human coronary artery endothelial cells [9].
• In cultured cell lines, Kaiso is found almost exclusively in the nucleus, where it generally acts as a transcriptional repressor [10].
• We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, delta-catenin, and myogenic transcription factors at the neuromuscular junction [1].
• Antibodies against Kaiso and delta-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction [1].
• However, the recent discovery of the nuclear BTB/POZ-ZF transcription factor Kaiso as a p120(ctn) binding partner, coupled with the detection of p120(ctn) in the nucleus of some cell lines and tumor tissues, suggested that like the classical beta-catenin, p120(ctn) undergoes nucleocytoplasmic trafficking and regulates gene expression [11].

Associations of ZBTB33 with chemical compounds

• Here we demonstrate that Kaiso, a methyl CpG binding protein belonging to the BTB/POZ family of transcription factors, is a component of the human N-CoR complex [5].
• Kaiso is a bimodal transcription factor that recognizes methylated CpG dinucleotides or a conserved unmethylated sequence (TNGCAGGA, the Kaiso binding site) [12].
• The mutation of one positively charged lysine to alanine in the NLS of full-length Kaiso significantly inhibited its nuclear localization in various cell types [13].

Other interactions of ZBTB33

• Detection of p120(ctn), Kaiso, and VE-cadherin mRNA was carried out using quantitative real time PCR [9].
• Quantitative real time PCR analysis revealed p120(ctn):GAPDH ratios, Kaiso: GAPDH ratios, and VE-cadherin:GAPDH ratios, relative to static control for each set, of 0.99-4.18 (mean +/- S.E., 1.94 +/- 0.404), 1.0-5.24 (2.11 +/- 0.51), and 0.99-1.42 (1.09 +/- 0.09) after 3 h of LSS, respectively [9].
• In vivo, Kaiso targets the N-CoR complex to the MTA2 gene promoter in a methylation-dependent manner [5].

Analytical, diagnostic and therapeutic context of ZBTB33

• When xenografted tumors were returned to cell culture, Kaiso was re-expressed and was once again found in the nucleus [10].
• To examine this phenomenon more carefully, tumor cells exhibiting strong nuclear Kaiso staining in vitro were injected into nude mice and grown as xenografts [10].
• To facilitate further study of Kaiso and to determine the physiological relevance of its interaction with p120(ctn), we have generated and characterized a panel of five Kaiso-specific monoclonal antibodies (MAbs) that function in immunoblotting, immunoprecipitation, and immunofluorescence analyses [14].
• Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay [1].

References