The CBX6 Knockout 786-O Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human 786-O renal epithelial cell line. This product disrupts the CBX6 gene, encoding a chromobox protein homolog 6 that acts as a transcriptional repressor within Polycomb repressive complex 1 (PRC1). The polyclonal format yields a heterogeneous cell pool with targeted gene disruption, enabling functional studies without clonal selection.
The parental 786-O cell line originates from a primary clear cell renal cell carcinoma and harbors a mutated VHL tumor suppressor gene, resulting in constitutive activation of hypoxia-inducible factor pathways. As a widely used model in kidney cancer research, 786-O cells recapitulate key aspects of renal epithelial malignancy and are particularly suited to studies of epigenetic gene regulation and drug response.
CBX6 functions as a reader of trimethylated histone H3 lysine 27 (H3K27me3) via its chromodomain, anchoring PRC1 at Polycomb target genes. It interacts with RING1B, BMI1, and PHC proteins to facilitate chromatin compaction and stable transcriptional repression through H2AK119 monoubiquitination. Upstream, the PRC2 complex??composed of EZH2, SUZ12, and EED??deposits H3K27me3 marks that recruit CBX6. Critical downstream targets repressed by this axis include the HOX cluster genes and the tumor suppressor CDKN2A. Thus, CBX6 bridges PRC2-mediated histone modification and PRC1-mediated gene silencing.
In the 786-O cell model, CBX6 knockout is expected to relieve PRC1-dependent silencing of CDKN2A and other differentiation-related genes, potentially impacting cell proliferation, tumorigenicity, and therapy response. This system is invaluable for examining how Polycomb-mediated epigenetic repression contributes to kidney cancer pathophysiology and for exploring the functional consequences of reactivating tumor-suppressive programs.
Applications encompass renal cell carcinoma epigenetics, investigation of tumor suppressor gene reactivation, and drug resistance studies. Typical assays include western blotting for CBX6 and PRC1 components, RT-qPCR for CDKN2A and HOX transcripts, ChIP-qPCR for H3K27me3 and CBX6 occupancy, and cell proliferation assays (MTT, BrdU). Colony formation, migration/invasion, and drug sensitivity profiling with sunitinib or everolimus further characterize the knockout phenotype. For additional information, please contact Ascent Research.
