Zbtb33, also known as Kaiso, is a multi-functional transcriptional regulator. It belongs to the BTB/POZ family and is involved in various biological processes. It can regulate cell division, apoptosis, and is abundant in the central nervous system. It is also associated with pathways like the Wnt/β -catenin signaling pathway [3]. Zbtb33 has been implicated in several diseases, such as clonal hematopoiesis, myelodysplastic syndromes, and multiple types of cancers, highlighting its biological importance [1,2,5,6,7,8].

In mouse models, Zbtb33 -edited hematopoietic stem and progenitor cells showed a competitive advantage in vivo and increased genome-wide intron retention, suggesting its role in clonal hematopoiesis and potentially linking DNA methylation and RNA splicing [1]. Zbtb33 gene knockout in mice led to increased locomotion, exploration, and pre -pulse inhibition. This was accompanied by reduced volumes of lateral ventricles and decreased norepinephrine concentration in the hypothalami and hippocampi, revealing its role in regulating behavior and the central nervous system [4]. In the developing mouse brain, Zbtb33 gene knockout changed the transcription of genes like Fgf9, Fgfr3, c -Myc, and FoxG1, which are related to the Wnt/β -catenin signaling pathway [3].

In conclusion, Zbtb33 is crucial for normal development, behavior, and proper functioning of the central nervous system. Its role in diseases such as clonal hematopoiesis and cancers is also significant. The use of Zbtb33 gene knockout mouse models has been instrumental in uncovering its functions in these biological processes and disease conditions, providing valuable insights into potential therapeutic targets for related disorders.

References:

1. Beauchamp, Ellen M, Leventhal, Matthew, Bernard, Elsa, Jaiswal, Siddhartha, Ebert, Benjamin L. 2021. ZBTB33 is mutated in clonal hematopoiesis and myelodysplastic syndromes and impacts RNA splicing. In Blood cancer discovery, 2, 500-517. doi:10.1158/2643-3230.BCD-20-0224. https://pubmed.ncbi.nlm.nih.gov/34568833/

2. Singhal, Sandeep K, Byun, Jung S, Park, Samson, Vohra, Nasreen, Gardner, Kevin. 2021. Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival. In Communications biology, 4, 150. doi:10.1038/s42003-021-01651-y. https://pubmed.ncbi.nlm.nih.gov/33526872/

3. Illarionova, N B, Borisova, M A, Bazhenova, E Y, Fursenko, D V, Kulikov, A V. . [Zbtb33 Gene Knockout Changes Transcription of the Fgf9, Fgfr3, с-Мус and FoxG1 Genes in the Developing Mouse Brain]. In Molekuliarnaia biologiia, 55, 422-430. doi:10.31857/S0026898421030095. https://pubmed.ncbi.nlm.nih.gov/34097677/

4. Kulikov, Alexander V, Korostina, Valeria S, Kulikova, Elizabeth A, Moshkin, Mikhail P, Prokhortchouk, Egor B. 2015. Knockout Zbtb33 gene results in an increased locomotion, exploration and pre-pulse inhibition in mice. In Behavioural brain research, 297, 76-83. doi:10.1016/j.bbr.2015.10.003. https://pubmed.ncbi.nlm.nih.gov/26454239/

5. Bernstein, Nicholas, Spencer Chapman, Michael, Nyamondo, Kudzai, Cohen, Robert L, Nangalia, Jyoti. 2024. Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis. In Nature genetics, 56, 1147-1155. doi:10.1038/s41588-024-01755-1. https://pubmed.ncbi.nlm.nih.gov/38744975/

6. Pozner, Amir, Terooatea, Tommy W, Buck-Koehntop, Bethany A. 2016. Cell-specific Kaiso (ZBTB33) Regulation of Cell Cycle through Cyclin D1 and Cyclin E1. In The Journal of biological chemistry, 291, 24538-24550. doi:10.1074/jbc.M116.746370. https://pubmed.ncbi.nlm.nih.gov/27694442/

7. Wang, Ligang, Ma, Jichao, Wang, Xiaoxiong, Ai, Jing, Zhao, Shiguang. 2018. Kaiso (ZBTB33) Downregulation by Mirna-181a Inhibits Cell Proliferation, Invasion, and the Epithelial-Mesenchymal Transition in Glioma Cells. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 48, 947-958. doi:10.1159/000491963. https://pubmed.ncbi.nlm.nih.gov/30036882/

8. Feng, Jing. 2017. Upregulation of MicroRNA-4262 Targets Kaiso (ZBTB33) to Inhibit the Proliferation and EMT of Cervical Cancer Cells. In Oncology research, 26, 1215-1225. doi:10.3727/096504017X15021536183526. https://pubmed.ncbi.nlm.nih.gov/28800784/