School of Medicine Publications and Presentations
Document Type
Article
Publication Date
6-4-2025
Abstract
Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso promoter-binding site—encode-derived Kaiso-binding site (eKBS) and many other transcription factors, including BRCA1. Here we sought to determine whether BRCA1 is a component of the Kaiso enhanceosome that regulates gene transcription. Using proximal ligation assays, immunoprecipitation followed by mass spectrometry, luciferase assays and ChIP-seq experiments, we evaluated the association between BRCA1 and Kaiso. Kaiso nuclear extract immunoprecipitation experiments revealed that Kaiso associates strongly with genes involved in RNA splicing and processing. When Kaiso was not crosslinked to DNA, BRCA1 was not detected among Kaiso-binding proteins. However, overexpression of BRCA1 increased Kaiso-mediated gene transcription in luciferase assays in a Kaiso-dependent manner. Comparison of BRCA1 ChIP-seq and Kaiso ChIP-seq data from HCT116 cells revealed both BRCA1 and Kaiso commonly bind to the promoters of 379 genes. The most enriched term associated with these genes where BRCA1 and Kaiso bind their promoters is metabolism of RNA. Disease processes associated with these BRCA1/Kaiso gene promoters indicate that BRCA1 is functionally linked to a Kaiso-directed programme of RNAP2-mediated gene transcription and likely associated with colorectal cancer development and maintenance.
Recommended Citation
Luo, W., Tripathi, M. K., Liu, Q., Chen, L., Cowan, R. W., Daniel, J. M., ... & Reynolds, A. B. (2025). Kaiso mediates transcription and RNA splicing in colorectal carcinoma: role of BRCA1 in the Kaiso enhanceosome. Open Biology, 15(6), 240329. https://doi.org/10.1098/rsob.240329
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Open Biology
DOI
10.1098/rsob.240329
Academic Level
faculty
Mentor/PI Department
Immunology and Microbiology
Comments
© 2025 The Author(s).
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.