KAT2B Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population, providing a loss-of-function model for the histone acetyltransferase KAT2B (P/CAF) in the human non-small cell lung adenocarcinoma cell line NCI-H1975. This product offers a heterogeneous gene-disrupted pool generated through CRISPR/Cas9-mediated disruption of the target gene, suitable for functional studies without clonal selection.
NCI-H1975 cells, derived from the pleural effusion of a patient with non-small cell lung carcinoma, harbor activating EGFR L858R and T790M mutations. These mutations drive constitutive signaling through MAPK and PI3K/AKT cascades and confer resistance to first- and second-generation EGFR tyrosine kinase inhibitors, establishing this line as a key model for EGFR-mutant lung adenocarcinoma research.
KAT2B encodes a histone acetyltransferase that acetylates lysine residues on histones H3 (K9, K14, K18) and H4 (K5, K8, K12), relaxing chromatin to facilitate transcription. It acts as a co-activator for transcription factors including p53, E2F1, and c-Myc, and directly acetylates p53 and c-Myc to modulate their stability and activity. Upstream regulators include p53, E2F1, c-Myc, CBP/p300, and MAPK signaling, while KAT2B interacts with CBP, p300, PCAF, TBP, TAFs, and nuclear receptors. This integrates signals from p53, Wnt, Notch, and TGF-beta pathways, regulating downstream targets such as CDKN1A, MYC, and CCND1 through promoter histone acetylation.
In the NCI-H1975 context, disruption of KAT2B impairs cell cycle progression and proliferation, and sensitizes cells to DNA damage by altering histone modification landscapes and p53 acetylation. This reveals epigenetic dependencies in mutant EGFR-driven lung adenocarcinoma, enabling dissection of how chromatin remodeling cooperates with oncogenic kinase signaling and influences drug resistance.
Applications include investigating epigenetic regulation in lung cancer, mechanisms of therapy resistance, and functional genomics of histone acetylation. Representative assays encompass Western blot for H3K9ac and H3K14ac, RT-qPCR for CDKN1A and MYC, cell proliferation and colony formation assays, ChIP-qPCR for histone marks, apoptosis and DNA damage assays, RNA-seq, and co-immunoprecipitation of acetylated p53. For further details, please contact Ascent Research.
