The KDM5C Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population in which the gene encoding the histone H3K4 demethylase KDM5C has been disrupted. This loss-of-function model provides a genetically defined system for investigating KDM5C-dependent epigenetic regulation and transcriptional repression. The polyclonal knockout pool is generated by target-gene disruption in the PaTu 8988t cell line, enabling functional studies without the isolation of single-cell clones.
The PaTu 8988t host cell line is a widely used in vitro model of metastatic pancreatic ductal adenocarcinoma. Established from a liver metastasis of a human pancreatic adenocarcinoma, these cells harbor an activating KRASG12V mutation and display an epithelial morphology. PaTu 8988t cells are well-characterized for studying pancreatic cancer biology, including tumor cell proliferation, migration, and drug response, making them a relevant background for interrogating epigenetic modifiers in this aggressive disease context.
KDM5C belongs to the JmjC domain-containing histone demethylase family and specifically catalyzes the removal of mono- and dimethyl marks from histone H3 lysine 4 (H3K4me1/me2). This activity compacts chromatin and represses transcription of target genes, including BDNF, SCN2A, CCNA2, and CCNB1. KDM5C is recruited by the transcription factor REST and forms co-repressor complexes with HDAC1/2, SIN3A, CoREST, and BHC80. Upstream regulation involves retinoic acid receptors and miRNA-138, positioning KDM5C at the intersection of chromatin remodeling, RET signaling, and cell cycle control.
In pancreatic adenocarcinoma, KDM5C is implicated in sustaining proliferative signaling, partly through repression of tumor suppressor loci. The PaTu 8988t knockout model therefore offers a physiologically relevant platform to dissect KDM5C’s role in epigenetic dysregulation that drives pancreatic cancer growth and metastasis. Additionally, because KDM5C mutations cause X-linked intellectual disability and are linked to autism spectrum disorder, this model may facilitate cross-context mechanistic studies, though the primary utility remains in pancreatic cancer research.
Typical applications include functional analysis of histone demethylation, epigenetic reprogramming in cancer, and drug target validation. Researchers can employ Western blotting to monitor global H3K4me1/me2 levels, RT-qPCR to measure re-expression of KDM5C-repressed genes, and ChIP-qPCR to assess histone mark dynamics at specific promoters. Phenotypic assays such as cell proliferation, colony formation, and migration can delineate the consequences of KDM5C loss. RNA-seq analyses further enable transcriptome-wide profiling. For further technical details, please contact Ascent Research.
