Abstract A032: Exploring ZBTB33 (KAISO) binding profiles in aggressive prostate cancer cells

Abstract Kaiso (ZBTB33), a member of the BTB/POZ zinc finger protein family, acts as a transcriptional repressor or activator by binding to specific DNA sequences known as Kaiso binding sites (KBS) or methylated CpG dinucleotides via its zinc finger domains. Kaiso overexpression and nuclear localization are associated with aggressive prostate cancer (PCa). In this study, we aimed to investigate the genomic distribution of Kaiso in both the androgen-sensitive LnCaP and androgen-insensitive C42B model, and LnCaP cells that are genetically engineered to overexpress Kaiso. Utilizing these models, we employed a multi-omics approach, including Cleavage Under Targets & Release Using Nuclease (CUT&RUN), RNA-seq, and Reduced Representation Bisulfite Sequencing (RRBS). CUT&RUN analysis revealed that Kaiso preferentially binds more to promoter regions of Kaiso-overexpressing LnCaP model and C42B (which is also overexpressing Kaiso) compared LnCaP src control. Integration of Kaiso-bound promoter regions from CUT&RUN with RNA-seq data identified 159 upregulated and 91 downregulated genes, using thresholds of |log2FC| > 1.3 and adjusted p-value < 0.2. Pathway enrichment analyses using KEGG and Gene Ontology (GO) databases indicated that these significantly differentially expressed kaiso-bound genes are involved in several biological processes, including growth factor binding and positive regulation of the MAPK cascade. Motif analysis reveals that androgen-insensitive C42B as well as Kaiso overexpressed LnCaP, have CGCG as a primary motif. Since Kaiso preferentially binds to methylated regions in the genome, we overlapped the Kaiso-bound promoter regions with RRBS-derived methylation data. In summary, our findings characterize the genomic binding preferences of Kaiso and highlight its potential regulatory role in transcription and cancer-related pathways. Citation Format: Shahjalal Chowdhury, Moray Campbell, Aliyu Muhammad, Isra Elhussin, Huixian Lin, Md Abu Talha. Siddique, Sazaul Morshed Sazib, Oceane Kircha. Nana, Balasubramanyam Karanam, Clayton Yates. Exploring ZBTB33 (KAISO) binding profiles in aggressive prostate cancer cells [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A032.