The H4C1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population of human renal carcinoma origin. This model introduces a targeted disruption of the H4C1 gene, which encodes histone H4, a core nucleosomal protein. The polyclonal format provides a heterogeneous pool of gene-edited cells, suited for loss-of-function analyses without clonal isolation.
The parental 786-O cell line is derived from a primary clear cell renal adenocarcinoma. These epithelial cells are VHL-deficient and express stabilized HIF-2??, recapitulating the pseudohypoxic state characteristic of clear cell renal cell carcinoma. They serve as a standard system for studying tumorigenesis, metastatic progression, and therapeutic resistance in ccRCC.
Histone H4 is essential for chromatin structure and epigenetic regulation. It assembles into nucleosomes with H2A, H2B, and H3, and its deposition involves chaperones CAF-1 and NAP1, as well as interactions with SWI/SNF chromatin remodelers. H4C1 expression is transcriptionally controlled by E2F factors and the NF-Y complex, and its function is coupled to CDK1/Cyclin B activity. Disruption of H4C1 leads to nucleosome destabilization, global chromatin decompaction, defective DNA repair, impaired cell cycle progression, and altered apoptosis regulators. Downstream effects are mediated through factors such as CAF-1, ASF1, HAT1, HDAC1, and SUV39H1, which modulate histone modifications and epigenetic states.
In the VHL-deficient 786-O background, H4C1 knockout provides a system to examine how core histone depletion influences ccRCC phenotypes. By disrupting nucleosome integrity, this model can unveil epigenetic vulnerabilities in proliferation, metastasis, and drug resistance pathways, and it may help identify synthetic lethal relationships with existing chromatin-targeting agents.
This product is suited for applications such as epigenetic profiling, functional genomics, and cancer drug screening. Assays include ChIP to map histone marks, RNA-seq for transcriptome analysis, Western blotting for histone quantification, cell proliferation and clonogenic assays, comet assay for DNA damage, immunofluorescence for chromatin structure, and flow cytometry for cell cycle. For further details, please contact Ascent Research.
