The HDAC8 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited human cell population targeting the HDAC8 gene in the NCI-H1299 lung adenocarcinoma epithelial line. This polyclonal knockout product comprises a heterogeneous pool of edited alleles, offering a loss-of-function model for functional genomics and drug screening applications without clonal selection. The gene-edited cells are derived from Homo sapiens and serve as a ready-to-use tool for epigenetic and cancer research.
NCI-H1299 is a widely used non-small cell lung cancer model isolated from a lymph node metastasis, characterized by a TP53-null genotype and wild-type KRAS. Its adherent, epithelial morphology and metastatic origin make it suitable for examining tumor cell invasion, migration, and proliferation. The cell line??s defined genetic background enables direct interrogation of HDAC8-dependent phenotypes in the absence of p53-mediated transcriptional control.
As a class I histone deacetylase, HDAC8 removes acetyl marks from histones H3 and H4, condensing chromatin and repressing transcription. It also targets non-histone substrates including SMC3, p53, and ERR??, thereby coordinating DNA repair, cell cycle progression, and metabolic signaling. HDAC8 function is regulated by transcription factors SP1 and E2F1, and its activity is modulated by CK2 phosphorylation. Downstream signal propagation involves altered expression of p21, c-Myc, Bcl-2, and modulation of epigenetic marks such as H3K9ac and H4K16ac. Through these interactions, HDAC8 integrates pathways like p53 signaling, Wnt/??-catenin, and Notch, influencing cell fate decisions.
In NCI-H1299 cells, HDAC8 disruption enhances acetylation of SMC3 and non-p53 targets, impairing sister chromatid cohesion and transcriptional programs critical for proliferation and metastasis. This polyclonal knockout model reveals HDAC8??s role in governing epithelial-mesenchymal transition (EMT), as evidenced by shifts in E-cadherin, N-cadherin, Snail, and Slug expression. The cell population also displays altered sensitivity to DNA-damaging agents and HDAC inhibitors, making it pertinent for studying therapeutic resistance. Moreover, the interaction with STAT3, CREB, and HSP70 further contextualizes HDAC8 in signal-dependent transcriptional regulation and protein stability networks.
This product supports diverse experimental workflows, including western blotting for HDAC8 and acetylated target proteins, RT-qPCR for EMT- and cell cycle-related gene expression, and ChIP-qPCR for genome-wide acetylation changes. Flow cytometric cell cycle and apoptosis assays, along with Transwell migration/invasion tests, enable functional assessment. Drug sensitivity profiling with HDAC inhibitors and transcriptome-wide RNA-seq analysis are feasible. For technical support or ordering details, please contact Ascent Research.
