The KAT7 Knockout PaTu 8988t Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population in which the KAT7 gene has been disrupted, offering a loss-of-function model for investigating KAT7-dependent processes in pancreatic cancer. Derived from the PaTu 8988t pancreatic ductal adenocarcinoma cell line, these polyclonal knockout cells allow researchers to study the impact of KAT7 deficiency in a genetically heterogeneous cell pool, recapitulating the inherent diversity of gene-edited populations without clonal selection.
The host cell line, PaTu 8988t, is a well-characterized human pancreatic ductal adenocarcinoma cell line originally isolated from a liver metastasis. Its aggressive metastatic origin and maintenance of ductal adenocarcinoma features make it a relevant model for pancreatic cancer research, particularly for studying tumor cell proliferation, drug resistance, and epigenetic regulation. The line is widely employed in xenograft and in vitro assays to evaluate therapeutic targets.
KAT7 (also known as HBO1) is a histone acetyltransferase that catalyzes acetylation of histone H4 at lysine residues, predominantly at replication origins, to promote the assembly of the pre-replicative complex. KAT7 is activated by cell cycle signals and the E2F1 transcription factor, and it functions within multisubunit complexes containing scaffold proteins such as JADE1/2/3 and BRPF1/2/3. Its enzymatic activity facilitates the recruitment of origin recognition complex (ORC) subunits, CDC6, and CDT1, enabling MCM2-7 helicase loading and replication licensing. By acetylating histone H4 at origins, KAT7 directly governs the chromatin environment required for accurate DNA replication initiation and cell cycle progression.
In the PaTu 8988t pancreatic cancer cell context, KAT7 disruption impairs replication licensing, leading to reduced CDT1 loading and MCM complex assembly at origins, which triggers a cell cycle arrest phenotype and diminished proliferative capacity. This model is particularly significant for dissecting the epigenetic mechanisms that sustain uncontrolled replication in pancreatic adenocarcinoma cells, where aberrant replication licensing contributes to genomic instability and tumor growth. The polyclonal knockout population enables assessment of heterogeneous responses to KAT7 loss, mimicking therapeutic targeting scenarios.
Researchers can employ this product in a range of applications, including EdU incorporation and flow cytometry-based cell cycle analyses to quantify proliferation defects, western blotting for acetyl-histone H4 to monitor KAT7 activity, and chromatin immunoprecipitation?CqPCR (ChIP-qPCR) at replication origins to evaluate pre-replicative complex assembly. Additionally, colony formation assays and gemcitabine sensitivity testing can be performed to explore synthetic lethal interactions and chemotherapeutic responses in the absence of KAT7. For additional information or to discuss custom applications, please contact Ascent Research.
