The H4C1 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human cervical carcinoma cell line Ca Ski. This product features targeted disruption of the H4C1 gene (also known as HIST1H4C), which encodes histone H4, a core nucleosome component. The polyclonal format provides a heterogeneous pool of knockout cells, each carrying distinct CRISPR/Cas9-mediated indels in the target locus, allowing investigation of H4C1 loss-of-function effects without the need for single-cell clone isolation.
The parental Ca Ski cell line is an adherent epithelial cell line derived from a cervical carcinoma metastasis. It is widely used as a model for HPV-16-driven oncogenesis, as it harbors integrated HPV-16 genomic DNA and constitutively expresses the viral oncoproteins E6 and E7, which disrupt the p53 and retinoblastoma tumor suppressor pathways, respectively. This background makes Ca Ski cells particularly suitable for studying the interplay between host chromatin regulation and viral oncogene expression.
Histone H4, encoded by H4C1, is an essential component of the nucleosome core particle, where it interacts with histones H2A, H2B, and H3 to form the octameric histone core. H4C1 expression is tightly regulated during the cell cycle, primarily by the CDK2/cyclin E kinase complex and the transcription factors E2F1 and NPAT, which coordinate histone gene transcription with DNA replication. The histone H4 protein serves as a substrate for multiple post-translational modifications, including acetylation and methylation, which are added by histone acetyltransferases and methyltransferases and recognized by chromatin remodelers and reader proteins. Histone H4 functions downstream of replication-dependent histone chaperones such as CAF-1 and ASF1, which facilitate its deposition onto newly replicated DNA. Through its structural role, H4 contributes to chromatin compaction, nucleosome stability, and the regulation of gene expression programs. H4C1 knockout is thus expected to disrupt these fundamental processes, leading to altered nucleosome assembly and chromatin organization.
In the Ca Ski cervical carcinoma model, loss of histone H4 function is anticipated to induce profound chromatin defects that may intersect with HPV-driven oncogenic pathways. The E6 and E7 oncoproteins are known to interact with epigenetic modulators and influence host gene expression; therefore, H4C1 knockout could affect the expression of viral oncogenes and cellular genes involved in proliferation and apoptosis. This model provides a valuable tool to dissect how histone deficiency impacts HPV-16-positive cancer cell biology, including potential effects on DNA replication stress, cell cycle progression, and sensitivity to epigenetic therapeutics.
These H4C1 knockout polyclonal cells are suitable for a wide range of applications in chromatin biology and cancer research. Typical assays include western blotting to confirm loss of H4 protein, RT-qPCR for assessing transcriptional changes, immunofluorescence to visualize chromatin alterations, and flow cytometry for analyzing cell cycle perturbations. Genomic approaches such as RNA-seq and ATAC-seq can reveal transcriptomic and chromatin accessibility changes upon H4C1 disruption, while ChIP-qPCR allows examination of specific histone modifications. Proliferation and apoptosis assays offer functional readouts of oncogenic signaling. Researchers studying HPV-host chromatin interactions, epigenetic dysregulation, or DNA replication stress will find this model instrumental. For further details, please contact Ascent Research.
