The BRD8 Knockout NCI-H1299 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population in which the BRD8 gene has been disrupted via CRISPR/Cas9-mediated gene editing. This polyclonal population comprises a heterogeneous mixture of edited alleles, providing a versatile loss-of-function model for investigating BRD8-dependent processes. The cells are derived from the NCI-H1299 human non-small cell lung carcinoma line and serve as a powerful tool for functional studies without the constraints of monoclonal isolation.
NCI-H1299 is a widely used human lung adenocarcinoma epithelial cell line originally isolated from a lymph node metastasis. As a tumorigenic model, it retains key features of non-small cell lung cancer, including aberrant chromatin regulation and dysregulated DNA damage responses. This genetic background is particularly relevant for dissecting the contributions of chromatin modifiers like BRD8 to lung cancer progression and therapy resistance.
BRD8 is a core subunit of the TIP60/NuA4 histone acetyltransferase complex, where it interacts with EP400, TRRAP, RUVBL1, RUVBL2, and the catalytic subunit TIP60 (KAT5). This complex acetylates histone H4 and H2A, thereby modulating chromatin architecture and facilitating transcriptional regulation. BRD8 is essential for NuA4 complex integrity and is activated by DNA damage signaling cascades involving ATM and ATR kinases. Downstream, BRD8-mediated acetylation promotes expression of genes involved in cell cycle arrest and apoptosis, linking chromatin remodeling directly to p53-dependent and independent tumor suppressor pathways.
In the context of NCI-H1299 lung adenocarcinoma cells, disruption of BRD8 compromises the TIP60/NuA4 complex, impairing histone acetylation and DNA repair proficiency. This knockout model enables researchers to examine how loss of BRD8 alters chromatin dynamics, gene expression, and cellular responses to genotoxic stress in a cancer-relevant setting. The polyclonal nature of the knockout population also allows assessment of phenotypic heterogeneity and selection pressures.
Applications include mechanistic studies of chromatin remodeling in cancer, DNA damage repair mechanisms, and functional genomics. Typical assays involve Western blotting for histone H4 acetylation, chromatin immunoprecipitation to map histone modification changes, immunofluorescence staining of DNA damage foci (??-H2AX), and cellular viability or colony formation assays to evaluate tumorigenic potential. This product is suitable for drug target validation and screening campaigns aimed at BRD8-associated malignancies. For further technical information, please contact Ascent Research.
