Description

The KDM5A Knockout HK-2 Cell Line is a CRISPR/Cas9-edited knockout cell line featuring targeted disruption of the KDM5A gene in the human HK-2 proximal tubule epithelial cell background. This model enables loss-of-function studies of KDM5A, a histone H3K4 demethylase involved in transcriptional repression. The cell line is supplied as a live culture and is designed for advanced epigenetic research.

HK-2 cells are an immortalized line derived from normal human kidney proximal tubule epithelium. They retain key differentiated functions such as polarized transport and metabolic activity, making them a standard model for renal physiology, drug transport, and injury responses. The well-characterized stable phenotype of HK-2 cells ensures reproducible experimental outcomes in studies of renal epithelial biology.

KDM5A functions as an H3K4me3 demethylase that represses gene expression. Its activity is regulated by upstream factors including HIF-1??, Notch intracellular domain, RB1, and miR-34a. KDM5A interacts with co-repressor complexes containing SIN3B, HDAC1, HDAC2, and REST. Key downstream targets include CCND1, CDKN1A, MYC, and CDH1, whose promoters it demethylates. Through these interactions, KDM5A integrates signals from hypoxia, Notch, and RB pathways to control cell cycle progression, differentiation, and epithelial function. For example, under hypoxia, HIF-1?? modulates KDM5A expression, affecting VEGF and EPO regulation.

Knockout of KDM5A in HK-2 cells abolishes H3K4me3 demethylation, leading to derepression of target genes and altered renal epithelial behavior. This model is particularly useful for investigating the epigenetic basis of renal responses to hypoxic stress, as occurs in acute kidney injury. It also provides a relevant system to study KDM5A??s role in renal cell carcinoma, where its dysregulation contributes to oncogenic reprogramming. The cell line thus offers insights into how chromatin modifications govern kidney cell fate and adaptation.

Researchers can employ this knockout cell line in a range of functional assays, including Western blotting, RT-qPCR, ChIP-qPCR, immunofluorescence, flow cytometry, and proliferation assays. Hypoxia exposure experiments and RNA-seq further enable dissection of KDM5A-dependent transcriptional networks. These applications support studies in epigenetic regulation, renal cancer modeling, and drug target validation. For inquiries and technical assistance, please reach out to Ascent Research.