The BRD3 Knockout SK-HEP-1 Polyclonal Cells product consists of a heterogeneous population of human SK-HEP-1 hepatocellular carcinoma cells that have been edited using CRISPR/Cas9 to disrupt the BRD3 gene. This polyclonal knockout cell pool provides a robust loss-of-function model for investigating the functional roles of the bromodomain-containing protein BRD3 in liver cancer biology. As a mixed population, it preserves the inherent genetic diversity of the edited bulk culture, making it suitable for pooled loss-of-function screens, bulk transcriptomic profiling, and drug sensitivity assays without the clonal selection bias that can arise from single-cell-derived knockouts.
The parental SK-HEP-1 cell line is an adherent epithelial line originally derived from the ascitic fluid of a male patient with liver adenocarcinoma. This well-characterized hepatocellular carcinoma model is widely employed in hepatic cancer research due to its stable growth characteristics, defined mutational landscape, and relevance to human liver tumor biology. SK-HEP-1 cells are particularly useful for studying the interplay between epigenetic regulators and oncogenic transcription in the hepatic microenvironment, making them an ideal host for BRD3 disruption.
BRD3 is a BET family chromatin reader that binds acetylated histone H4 marks, particularly H4K5ac and H4K8ac, deposited by CREBBP/EP300 acetyltransferases. Its bromodomains recruit P-TEFb (CDK9/Cyclin T1) to gene promoters, stimulating RNA Polymerase II elongation of oncogenes including MYC, CDK6, BCL2, and CCND1. BRD3 also interacts with NF-??B transcription factors and the Mediator subunit MED1, linking extracellular signals to transcriptional activation and driving cell proliferation and survival.
In hepatocellular carcinoma, BET proteins including BRD3 are frequently implicated in sustaining aberrant transcriptional programs that drive tumor growth. The SK-HEP-1 polyclonal BRD3 knockout model enables researchers to dissect the specific contributions of BRD3 to MYC-driven oncogenesis in a liver cell context, distinguishing it from the roles of BRD2 and BRD4. This model is also valuable for exploring epigenetic drug resistance, as BET inhibitors like JQ1 may exhibit differential sensitivity, and for identifying synthetic lethal partners in hepatic cancer.
Typical applications include RNA-seq expression profiling, ChIP-qPCR analysis of histone acetylation at target promoters, proliferation and colony formation assays, and flow cytometric apoptosis detection with Annexin V. The polyclonal knockout population is also suitable for high-throughput BET inhibitor screening, RT-qPCR validation of downstream targets, Western blot confirmation of BRD3 ablation, and MTT-based viability measurements. By enabling functional dissection of BET-dependent pathways, this model advances the development of targeted epigenetic therapies in liver cancer. For further details, please contact Ascent Research.
