The KDM5D Knockout UM-UC-3 Polyclonal Cells are a polyclonal cell population generated by CRISPR/Cas9-mediated disruption of the KDM5D gene in the UM-UC-3 human bladder carcinoma cell line. This loss-of-function model retains the polyclonal heterogeneity of the edited pool, avoiding clonal selection artifacts and providing a robust tool for studying gene function in a bladder cancer context.
The UM-UC-3 cell line is derived from a male patient with bladder transitional cell carcinoma, a high-grade invasive epithelial cancer. Widely used in bladder cancer research, these cells recapitulate key features of the disease, including aberrant signaling and epigenetic dysregulation. Their male origin is essential for investigating the Y-linked gene KDM5D, which is exclusively expressed in males.
KDM5D encodes a lysine-specific demethylase that specifically removes methyl groups from di- and trimethylated histone H3 lysine 4 (H3K4me2/me3), leading to transcriptional repression via chromatin condensation. KDM5D is activated by androgen receptor signaling and retinoic acid receptor pathways, and it interacts with HDAC1/2, SIN3A, and the CoREST complex to recruit additional repressive activities. It functions antagonistically to MLL complexes, which deposit H3K4 methylation. Key target genes silenced by KDM5D include HOX gene clusters and the cell cycle inhibitor CDKN1A, as well as spermatogenesis-related loci. In the knockout, loss of KDM5D results in increased H3K4 methylation and transcriptional derepression of these genes, thereby altering cellular programs.
In bladder carcinoma, KDM5D depletion is of particular interest because it may reactivate tumor suppressor genes or modulate oncogenic pathways controlled by H3K4 methylation dynamics. The UM-UC-3 knockout model enables exploration of KDM5D’s impact on epithelial cell proliferation, migration, and apoptosis, as well as sensitivity to drugs targeting androgen receptor or retinoic acid signaling. Moreover, since KDM5D is Y-chromosome-encoded and male-specific, this model offers unique opportunities to study sex-linked epigenetic vulnerabilities in cancer.
This polyclonal knockout product is ideally suited for a wide array of experimental applications, including chromatin immunoprecipitation (ChIP-qPCR or ChIP-seq) for mapping H3K4me3 distribution, quantitative RT-PCR and RNA-seq for gene expression profiling, and western blotting for protein analysis. Functional assays such as proliferation, migration/invasion, and drug response screens can be conducted to characterize phenotypic outcomes. The polyclonal format is particularly advantageous for pooled screening approaches and for assessing heterogeneous drug responses. For further technical information, please contact Ascent Research.
