The HDAC1 Knockout 786-O Polyclonal Cells constitute a CRISPR/Cas9-mediated gene-disrupted population derived from the Homo sapiens 786-O renal epithelial cell line. This knockout product is supplied as a heterogeneous pool of polyclonal cells, each harboring targeted disruption of the HDAC1 gene, enabling loss-of-function studies without single-cell cloning. The unfractionated format preserves biological variability inherent to pooled editing events, offering a cost-effective and physiologically relevant model for investigating HDAC1-dependent pathways in renal cancer.
The parental 786-O line originates from a human clear cell adenocarcinoma of the kidney and carries a well-characterized von Hippel-Lindau (VHL) tumor suppressor mutation. These adherent epithelial cells are extensively employed in renal cell carcinoma research, including studies on hypoxia response, tumor metabolism, and drug resistance. The VHL-deficient background couples with HDAC1 knockout to interrogate epigenetic mechanisms underlying malignant progression in a clinically relevant renal cancer context.
HDAC1 encodes a class I histone deacetylase that catalyzes removal of acetyl groups from lysine residues on histone H3 and H4, as well as non-histone substrates such as p53, STAT3, NF-??B, and E2F transcription factors. Acting within multiprotein complexes like NuRD, Sin3A, and CoREST, HDAC1 functions as a transcriptional corepressor to compact chromatin and silence target gene expression. Its activity is induced by upstream regulators including SP1, MYC, E2F factors, growth factor stimulation, and hypoxia. Mechanistically, HDAC1 interacts with Sin3A, MTA1/2, RbAp46/48, and CHD4 to repress promoters such as CDKN1A (p21) via histone deacetylation, and deacetylates p53 to diminish p21 expression, thereby promoting cell cycle progression and proliferation.
In the 786-O VHL-mutant renal cancer setting, HDAC1 disruption leads to hyperacetylation of histones and non-histone proteins, relieving transcriptional repression of tumor suppressor genes. This model is particularly significant for dissecting the crosstalk between epigenetic silencing and VHL loss in clear cell carcinoma. The knockout is anticipated to impair cell proliferation, enhance apoptosis, and sensitize cells to HDAC inhibitor compounds such as vorinostat and romidepsin, making it a relevant platform for preclinical drug evaluation. Additionally, the polyclonal nature allows assessment of population-level responses that mirror tumor heterogeneity.
User applications include western blotting for histone acetylation markers, RT-qPCR for downstream targets like CDKN1A and p53-regulated genes, ChIP-qPCR to examine promoter occupancy, and HDAC enzymatic activity assays. Functional readouts such as MTT/CCK-8 proliferation, Annexin V apoptosis, and drug sensitivity testing with FDA-approved HDAC inhibitors are integral to mechanistic and translational studies. RNA-seq transcriptome analysis further enables global epigenetic reprogramming investigations. For further technical specifications and ordering information, please contact Ascent Research.
