The JADE3 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population designed to disrupt JADE3 gene function in the human NCI-H1975 lung adenocarcinoma cell line. This loss-of-function model provides a versatile tool for investigating JADE3, a scaffold protein in the HBO1 histone acetyltransferase complex that regulates transcription via histone H4 acetylation. The polyclonal knockout format ensures a heterogeneous population, avoiding clonal artifacts.
NCI-H1975 is a non-small cell lung cancer cell line derived from a lung adenocarcinoma patient. It carries the EGFR L858R activating mutation and the T790M gatekeeper mutation, conferring sensitivity and acquired resistance to EGFR tyrosine kinase inhibitors. This genetic background makes the cell line highly relevant for studying oncogenic signaling and drug resistance mechanisms.
JADE3 acts as a scaffold within the HBO1 (KAT7) complex, interacting with ING4, ING5, EAF6, and the catalytic subunit KAT7 to acetylate histone H4 at lysines 5, 8, and 12. This acetylation promotes transcription of genes critical for cell cycle progression and DNA replication. JADE3 functions downstream of E2F1 and is essential for complex integrity and activity, so knockout of JADE3 reduces H4 acetylation and impairs proliferative gene expression programs.
In the NCI-H1975 background, which harbors EGFR L858R and T790M mutations, JADE3 knockout allows dissection of how histone acetylation dynamics intersect with oncogenic EGFR signaling. This model can reveal whether HBO1-mediated epigenetic modifications are necessary for sustaining proliferation and acquired drug resistance, and it may identify epigenetic dependencies that could be targeted alongside EGFR inhibitors to improve therapeutic outcomes.
This polyclonal knockout cell population is suitable for diverse functional assays, including western blotting to confirm JADE3 loss and changes in H4 acetylation, RT-qPCR to measure downstream gene expression, ChIP-qPCR to profile histone modifications at specific loci, and cell viability or colony formation assays to assess proliferation. Drug sensitivity studies using EGFR tyrosine kinase inhibitors, such as osimertinib, can elucidate JADE3’s role in resistance, while histone acetyltransferase activity assays directly probe HBO1 complex function. Thus, these cells support advanced research into epigenetic regulation, lung cancer biology, and drug resistance. For further details, please contact Ascent Research.
