The PAGR1 Knockout AGS Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma epithelial cell line. This heterogeneous pool of knockout cells stably disrupts PAGR1 gene function, avoiding clonal selection artifacts and enabling robust functional analyses. The mixed population collectively ablates PAGR1, facilitating studies of its scaffolding role within MLL3/MLL4 complexes and its impact on H3K4 methylation and gene regulation in a gastric cancer context.
The AGS cell line, derived from a primary gastric adenocarcinoma, is a widely utilized in vitro model that retains key features of gastric cancer biology, including aberrant growth signaling and dysregulated epigenetic landscapes. These epithelial cells are routinely employed to investigate mechanisms of tumor progression, invasion, and drug resistance. Their compatibility with standard culture conditions and CRISPR editing facilitates reproducible knockout studies, enabling precise dissection of gene function in a physiologically relevant gastric cancer context. As a host for PAGR1 knockout, AGS cells provide a pertinent system to study epigenetic and transcriptional contributions to gastric adenocarcinoma, where chromatin remodeling pathways are frequently altered.
PAGR1 functions as an essential scaffold protein within the MLL3/MLL4 (KMT2C/KMT2D) histone methyltransferase complexes, which catalyze H3K4 monomethylation and dimethylation at enhancers and promoters. It directly interacts with PAXIP1/PTIP, linking DNA damage signaling to this enzymatic machinery, and associates with core subunits such as ASH2L, RBBP5, WDR5, and DPY30. The complex also recruits KDM6A/UTX, coordinating H3K4 methylation dynamics to regulate transcriptional activation of genes controlling proliferation, differentiation, and DNA repair. Upstream DNA damage signals trigger PAXIP1-dependent recruitment of PAGR1-containing complexes to chromatin, thereby coupling genomic stress to H3K4 methylation and transcriptional responses.
In AGS gastric adenocarcinoma cells, PAGR1 knockout disrupts MLL3/MLL4 complex integrity and impairs H3K4 methylation at target loci, leading to altered expression of cell cycle regulators and differentiation factors. This epigenetic dysfunction attenuates oncogenic transcriptional programs, compromising cellular proliferation, migration, and viability under genotoxic stress. Consequently, PAGR1-deficient AGS cells serve as a powerful tool for dissecting the interplay between epigenetic regulation and gastric adenocarcinoma pathology, revealing potential synthetic vulnerabilities exploitable by epigenetic therapies.
Researchers can utilize this polyclonal knockout population in diverse assays, including ChIP-qPCR or CUT&RUN for histone modification profiling, RNA-seq transcriptomics, Western blotting for H3K4 methylation changes, and functional assays such as proliferation, colony formation, migration, and drug sensitivity testing. The model is suited for functional genomics screens and drug target validation, particularly for epigenetic therapies in gastric cancer. Its polyclonal nature supports high-throughput approaches and facilitates the generation of derivative cell lines with additional modifications. For further technical details or ordering information, please contact Ascent Research.
