The HAT1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the HAT1 gene. This product provides a loss-of-function model for studying HAT1 biology in a human lung adenocarcinoma background. The polyclonal population contains a heterogeneous pool of edited cells, offering a physiologically relevant spectrum of mutations for functional studies without clonal artifacts. These cells are suitable for immediate use in downstream assays such as western blotting, qPCR, and proliferation analyses.
The parental NCI-H1975 cell line is a well-characterized model of non-small cell lung adenocarcinoma derived from a non-smoking female patient. These cells harbor endogenous EGFR L858R and T790M mutations, conferring sensitivity to first- and third-generation EGFR tyrosine kinase inhibitors. The line is extensively used to study acquired resistance to EGFR-targeted therapies and to screen novel therapeutic agents. The NCI-H1975 background provides a clinically relevant context for examining the role of chromatin modifiers in oncogenic signaling and drug response.
HAT1 encodes a type B histone acetyltransferase that acetylates newly synthesized histone H4 on lysines K5 and K12. This modification is critical for chromatin assembly during DNA replication, facilitating histone deposition by chaperones ASF1A/B and CAF-1 complex. HAT1 forms a complex with HAT2 (RBBP7/RbAp46) and histone H4 to mediate nucleosome assembly. Its activity is regulated by E2F transcription factors and RB1, linking chromatin assembly to cell cycle. HAT1-mediated H4 acetylation shapes chromatin structure and gene expression, affecting proliferation and survival.
In the NCI-H1975 lung adenocarcinoma model, HAT1 knockout disrupts the normal pattern of histone H4 acetylation, potentially altering nucleosome assembly and global chromatin organization. Given the dependence of cancer cells on epigenetic plasticity for proliferation and drug adaptation, loss of HAT1 may perturb cell cycle progression and sensitize cells to EGFR inhibitors. This knockout system enables dissection of how HAT1-dependent chromatin dynamics intersect with mutant EGFR-driven oncogenic pathways. Moreover, it can reveal synthetic lethal interactions exploitable for targeted therapy in lung adenocarcinoma.
These polyclonal knockout cells support western blotting, RT-qPCR, ChIP-qPCR, and colony formation assays to assess HAT1 loss. They enable EGFR inhibitor drug sensitivity profiling, RNA-seq, and synthetic lethality screens. The model is ideal for dissecting epigenetic contributions to lung adenocarcinoma progression and therapy resistance. For further details, contact Ascent Research.
