KAT7 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population targeting the human KAT7 gene in the NCI-H1703 lung squamous cell carcinoma cell line. This polyclonal cell product provides a loss-of-function model for studying KAT7 (HBO1), a histone acetyltransferase critical for DNA replication licensing and chromatin regulation. The polyclonal format preserves genetic heterogeneity, enabling robust experiments without clonal selection bias.
The parental NCI-H1703 cell line was derived from primary lung squamous cell carcinoma of a male smoker and serves as a well-characterized model of non-small cell lung cancer (NSCLC). These adherent epithelial cells retain key squamous features and oncogenic mutations, making them suitable for investigating molecular mechanisms of lung carcinogenesis and therapeutic responses.
KAT7 (HBO1/MYST2) functions as the catalytic subunit of an acetyltransferase complex containing ING4/ING5, JADE1/2/3, and Eaf6, which acetylates histone H3K14 and H4K5/12. Upstream, KAT7 is activated by Cdc6, Cyclin E/CDK2, and c-Myc, linking its activity to cell cycle progression. Downstream, KAT7-mediated acetylation facilitates loading of the MCM2?C7 helicase through interactions with Cdt1 and Mcm2, enabling DNA replication initiation. Direct acetylation targets include H3K14ac and H4K5ac, and KAT7 regulates cyclin A2 expression. Disruption of KAT7 impairs the Cdc6 ?? KAT7 ?? histone acetylation ?? MCM loading pathway, causing defective replication licensing, replication stress, and altered gene expression. KAT7 also intersects with the Notch signaling pathway, further influencing proliferation.
In NCI-H1703 cells, KAT7 knockout enables dissection of its role in sustaining lung squamous cell carcinoma phenotypes. Loss of KAT7 may sensitize cells to replication stress, revealing therapeutic vulnerabilities. This model also supports studies of chromatin modification and its impact on cancer-related gene expression. Given KAT7??s involvement in acute myeloid leukemia and breast cancer, this system may inform broader oncological research.
Applications include functional studies of KAT7 in lung cancer, DNA replication licensing assays, drug target validation, and high-throughput screening for KAT7 inhibitors. Representative techniques include western blotting, RT-qPCR, ChIP-qPCR for H3K14ac, flow cytometry-based cell cycle analysis, DNA replication assays, and colony formation. For technical inquiries, contact Ascent Research.