The HP1BP3 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 lung adenocarcinoma cell line. This product provides a pool of edited cells with targeted disruption of the HP1BP3 gene, encoding a chromatin-associated protein involved in heterochromatin organization and DNA damage repair. The polyclonal format ensures genetic diversity while enabling population-level loss-of-function studies. CRISPR/Cas9-mediated gene disruption preserves the endogenous cellular context, making these cells suitable for investigating HP1BP3 function in cancer biology.
The NCI-H1975 host cell line is an adherent epithelial model isolated from the pleural effusion of a female lung adenocarcinoma patient. It carries EGFR L858R and T790M mutations, conferring resistance to first-generation EGFR inhibitors, and serves as a well-characterized system for studying EGFR-mutant non-small cell lung cancer. This background recapitulates key aspects of therapeutic resistance, providing a relevant platform to examine how HP1BP3 loss impacts chromatin biology and drug sensitivity in a clinically representative context.
HP1BP3 functions as a chromatin-binding protein that interacts with heterochromatin protein 1 isoforms (HP1??/CBX5, HP1??/CBX1, HP1??/CBX3) and H3K9me3-modified histones to maintain heterochromatin architecture. It acts downstream of ATM and the transcription factor E2F1, linking DNA damage signaling and cell cycle regulation to chromatin organization. HP1BP3 facilitates chromatin compaction and recruits DNA repair factors such as 53BP1 to double-strand breaks. Disruption of HP1BP3 impairs these processes, compromising heterochromatin integrity and DNA repair fidelity, which can lead to genomic instability.
In the NCI-H1975 background, HP1BP3 knockout provides a model to investigate how chromatin-associated proteins influence genomic stability and drug response in EGFR-mutant lung adenocarcinoma. Loss of HP1BP3 may enhance DNA damage accumulation and perturb cell cycle checkpoints, potentially modulating sensitivity to genotoxic agents or targeted therapies. This system is particularly useful for dissecting epigenetic contributions to drug resistance and identifying new vulnerabilities in lung cancer cells.
Typical applications include Western blotting and RT-qPCR for target expression validation, immunofluorescence and ??H2AX foci assays for DNA damage assessment, and cell cycle and apoptosis analyses to evaluate proliferation and death. Colony formation assays measure clonogenic survival, while RNA-seq enables transcriptome-wide profiling of gene expression changes. These tools support research areas such as cancer epigenetics, DNA damage response, lung adenocarcinoma biology, and functional genomics. For further details, please contact Ascent Research.
