Baz1b, also known as bromodomain adjacent to the zinc finger domain 1B or Williams syndrome transcription factor (WSTF), is encoded by the WBSCR9 gene. It is a versatile nuclear protein with a central role in chromatin remodeling through two distinct complexes. It is also involved in DNA replication and repair, transcriptional processes involving RNA Polymerases I, II, and III, and possesses kinase activity [1].

In mouse models, homozygous Baz1btm2a(KOMP)Wtsi mutant mice die shortly after birth, and both homozygous mutants and heterozygotes are smaller than wild-type littermates. Heterozygotes and homozygous mutants are more likely to die than wild-type mice. Baz1b+/- mice exhibit a dilated cardiomyopathy, suggesting that Baz1b dosage may contribute to early death, decreased somatic growth, and cardiac abnormalities [2]. In zebrafish, baz1b loss-of-function leads to mild underdevelopment at larval stages, distinctive craniofacial features, reduced anxiety-associated phenotypes, and altered social behaviors, recapitulating phenotypes associated with the domestication syndrome [3]. In colorectal cancer, BAZ1B is overexpressed and contributes to cell proliferation in vitro and in vivo, supporting its emerging oncogenic role [4]. In thyroid cells, downregulation of BAZ1B leads to decreased cell viability and survival, suggesting it could be responsible for thyroid defects in some Williams syndrome patients [5].

In conclusion, Baz1b is essential for multiple biological processes. Studies using gene knockout models in mice and zebrafish have revealed its role in cardiovascular function, development, behavior, and disease, such as cardiomyopathy, domestication-related phenotypes, and cancer. These findings enhance our understanding of the biological functions of Baz1b and its implications in various disease conditions.

References:

1. Sharif, Shahin Behrouz, Zamani, Nina, Chadwick, Brian P. 2021. BAZ1B the Protean Protein. In Genes, 12, . doi:10.3390/genes12101541. https://pubmed.ncbi.nlm.nih.gov/34680936/

2. McIntosh, Basil, Knutsen, Russell, Levin, Mark, Heuckeroth, Robert, Kozel, Beth. . Baz1b Dosage Influences Cardiovascular Function, Predisposing to Dilated Cardiomyopathy. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36 Suppl 1, . doi:10.1096/fasebj.2022.36.S1.R2293. https://pubmed.ncbi.nlm.nih.gov/35723872/

3. Torres-Pérez, Jose V, Anagianni, Sofia, Mech, Aleksandra M, Vallortigara, Giorgio, Brennan, Caroline H. 2022. baz1b loss-of-function in zebrafish produces phenotypic alterations consistent with the domestication syndrome. In iScience, 26, 105704. doi:10.1016/j.isci.2022.105704. https://pubmed.ncbi.nlm.nih.gov/36582821/

4. Grochowska, Aleksandra, Statkiewicz, Malgorzata, Kulecka, Maria, Ostrowski, Jerzy, Mikula, Michal. 2022. Evidence supporting the oncogenic role of BAZ1B in colorectal cancer. In American journal of cancer research, 12, 4751-4763. doi:. https://pubmed.ncbi.nlm.nih.gov/36381331/

5. Allegri, Lorenzo, Baldan, Federica, Mio, Catia, Amendola, Elena, Damante, Giuseppe. 2020. BAZ1B is a candidate gene responsible for hypothyroidism in Williams syndrome. In European journal of medical genetics, 63, 103894. doi:10.1016/j.ejmg.2020.103894. https://pubmed.ncbi.nlm.nih.gov/32081709/