Alternative titles; symbols
HGNC Approved Gene Symbol: ZBTB4
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,459,378-7,484,249 (from NCBI)
By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2000) cloned ZBTB4, which they designated KIAA1538. RT-PCR ELISA detected moderate to high expression in all adult and fetal tissues examined. Highest expression was detected in adult heart, brain, ovary, and spinal cord, in fetal brain, and in all specific adult brain regions examined.
By searching the human genome for sequences encoding KAISO (300329)-like triple zinc finger domains, Filion et al. (2006) identified ZBTB4 and ZBTB38 (612218). The deduced 1,013-amino acid ZBTB4 protein contains an N-terminal BTB/PPZ domain followed by 4 zinc fingers, a proline-rich domain, a glutamate-rich domain, 2 additional zinc fingers, and an additional C-terminal proline-rich region. The BTB/POZ domain of ZBTB4 is interrupted by a 60-amino acid stretch, and the N-terminal zinc finger region of ZBTB4 contains the KAISO-like triple zinc finger domain. Northern blot analysis detected Zbtb4 in all mouse tissues examined, with highest expression in brain, lung, kidney, muscle, and heart. In situ hybridization of mouse brain detected Zbtb4 mainly in neurons. Expression was highest in hippocampus, in structures involved in olfaction, in arcuate nuclei, in motor nuclei of the brainstem, and in granular layer of the cerebellum. Upon transfection into mouse fibroblasts, ZBTB4 and ZBTB38 localized to chromocenters, which are heavily methylated chromosome aggregates found in mouse, but not human, cells; however, their positions did not completely overlap. Both proteins had a more diffuse nuclear localization in mouse cells impaired in DNA methylation.
Using a gel retardation assay, Filion et al. (2006) showed that the isolated zinc finger domains of KAISO, ZBTB4, and ZBTB38 bound methylated CpGs, and that all 3 proteins repressed the expression of a methylated reporter gene. ZBTB4 lacking the KAISO-like zinc fingers was inactive. ZBTB4, but not ZBTB38, also bound the KAISO-binding sequence TCCTGCNA. Filion et al. (2006) also showed that the zinc finger domains of ZBTB4 and ZBTB38 homo- and heterodimerize.
By radiation hybrid analysis, Nagase et al. (2000) mapped the ZBTB4 gene to chromosome 17.
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]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 143-150, 2000. [PubMed: 10819331] [Full Text: https://doi.org/10.1093/dnares/7.2.143]