This product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human CAL-27 tongue squamous cell carcinoma line, with targeted disruption of the H4C1 gene. H4C1 encodes histone H4, a core nucleosomal protein critical for chromatin architecture and gene regulation. The polyclonal format provides a heterogeneous pool of edited cells, enabling robust functional assessment of H4C1 loss without clonal isolation. This model is designed for investigating histone H4 functions in oral cancer and chromatin biology.
The CAL-27 cell line originates from a 56-year-old male with tongue squamous cell carcinoma and displays adherent epithelial morphology. It is a well-established model for head and neck cancer, retaining dysregulated cell cycle and chromatin features characteristic of aggressive tumors. CAL-27 cells are extensively utilized to study tumor biology, drug responses, and epigenetic mechanisms in squamous cell carcinomas, making them an appropriate host for dissecting histone-dependent processes.
Histone H4, encoded by H4C1, is a central component of the nucleosome, forming the histone octamer with H2A, H2B, and H3. Its cell cycle-dependent transcription is driven by the NPAT coactivator downstream of the Cyclin E/CDK2 complex and E2F1. H4C1 knockout abrogates histone H4 protein production, impairing nucleosome assembly by chaperones ASF1 and CAF-1 and disrupting chromatin remodeling by SWI/SNF complexes. Downstream, altered expression of cell cycle regulators such as CDKN1A triggers checkpoint activation, leading to reduced proliferation and apoptosis. This loss-of-function model reveals the essential role of histone H4 in maintaining genomic stability and proper gene expression.
In the CAL-27 oral cancer context, H4C1 knockout serves to elucidate the dependency of squamous cell carcinomas on intact nucleosome dynamics. Tumor cells often exploit histone modifications and chromatin plasticity for survival; disruption of core histone supply destabilizes oncogenic transcriptional networks. This model facilitates testing of epigenetic drug sensitivities, including HDAC inhibitors, and exploration of synthetic lethal interactions targeting DNA repair pathways compromised by histone loss.
Typical applications include Western blotting and RT-qPCR to validate H4C1 knockout and expression of downstream targets, flow cytometry for cell cycle profiling, and immunofluorescence for chromatin structure analysis. Advanced studies may employ RNA-seq and ChIP-seq to map transcriptomic and epigenomic changes. Apoptosis assays and DNA replication stress evaluations further characterize functional outcomes. HDAC inhibitor sensitivity testing provides pharmacological insights. For more information, please contact Ascent Research.
