The KDM6A Knockout A-549 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function studies of the KDM6A gene. This polyclonal pool, derived from the A-549 lung adenocarcinoma cell line, carries heterogeneous KDM6A gene disruptions, enabling population-based analyses without clonal selection. The product is ideal for investigating KDM6A-dependent epigenetic regulation in a KRAS-mutant background.
A-549 is a human lung adenocarcinoma cell line with epithelial morphology, originally isolated from a 58-year-old male. It harbors a KRAS G12S mutation and wild-type p53, making it a key model for studying KRAS-driven oncogenesis and type II pneumocyte biology. This genetic background provides a relevant context to explore the interplay between oncogenic KRAS signaling and chromatin-modifying enzymes such as KDM6A.
KDM6A (UTX) is a histone demethylase specific for H3K27me2/me3, opposing PRC2-mediated repression. As a subunit of the MLL3/MLL4 COMPASS complexes, it cooperates with ASH2L, WDR5, RBBP5, and DPY30 to activate transcription. Upstream signals from RAR, ESR1, and NICD recruit KDM6A to chromatin, where it facilitates expression of HOXA genes, CDKN1A (p21), and other tumor suppressors. It also interacts with SMAD2/3 and NCOA6 to mediate TGF-?? and retinoic acid responses.
In the A-549 lung adenocarcinoma model, loss of KDM6A leads to increased H3K27me3 at promoters of target genes, reinforcing transcriptional silencing of tumor suppressors and epithelial differentiation factors. This epigenetic reprogramming may promote oncogenic phenotypes, providing a valuable system to dissect KDM6A??s role as a tumor suppressor in KRAS-mutant lung cancer. The model enables investigation of how KDM6A deficiency collaborates with oncogenic KRAS to influence cancer progression and therapeutic response.
The KDM6A Knockout A-549 Polyclonal Cells are suitable for chromatin immunoprecipitation (ChIP-qPCR/ChIP-seq) to map H3K27me3 and H3K4me3 changes, gene expression profiling by RNA-seq or RT-qPCR, and protein analysis by Western blotting for KDM6A and global histone modifications. Functional assays such as proliferation, apoptosis, migration, and invasion studies, alongside drug sensitivity screening with epigenetic inhibitors or chemotherapeutics, can be readily performed. These cells support research into epigenetic regulation, TGF-??/retinoic acid/Notch signaling, and lung adenocarcinoma biology. For additional information or custom inquiries, please contact Ascent Research.
