The KDM1B Knockout HCT 116 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human HCT 116 colorectal carcinoma line. This product provides a heterogeneous loss-of-function model in which the KDM1B gene is disrupted, eliminating the encoded histone demethylase. As a polyclonal population, it avoids clonal artifacts and offers a robust tool for probing epigenetic regulation without single-cell selection.
The HCT 116 host line is a widely used epithelial colorectal carcinoma model characterized by a KRAS G13D activating mutation, high microsatellite instability (MSI-H), and defective DNA mismatch repair. These genetic traits recapitulate features of aggressive sporadic and hereditary colorectal cancers, making the line particularly suited for studying epigenetic mechanisms within a clinically relevant, oncogene-driven context.
KDM1B (also known as AOF1) functions as a lysine-specific demethylase that selectively removes mono- and di-methyl marks from histone H3 lysine 4 (H3K4me1/2), thereby repressing transcription. It operates within co-repressor complexes containing RCOR1, HDAC1, and HDAC2, often recruited by REST. Upstream, Notch signaling activates KDM1B by promoting proteolytic release of the Notch intracellular domain (NICD), while KDM1B feeds back to silence NOTCH1 and HOX gene clusters, as well as imprinted loci. Cross-talk with KDM1A and MLL complexes further integrates KDM1B into broader chromatin remodeling networks.
In the HCT 116 background, KDM1B knockout is expected to abolish its demethylase activity, leading to elevated H3K4me1/2 at target promoters and derepression of genes governed by KDM1B-containing complexes. Given the interplay between the KRAS-driven oncogenic signaling and epigenetic plasticity, this model permits dissection of how loss of KDM1B-mediated silencing alters proliferation, apoptosis, and stem-like phenotypes, unveiling context-dependent vulnerabilities in colorectal cancer.
This polyclonal knockout cell population is well-suited for chromatin immunoprecipitation (ChIP-qPCR) to map H3K4 methylation changes, Western blotting to confirm KDM1B depletion, and RT-qPCR or RNA-seq to quantify transcriptional alterations at targets such as HOX family members and NOTCH1. Functional analyses can be performed via colony formation, apoptosis and cell cycle flow cytometry, and drug sensitivity screens to assess roles in cancer stem cell maintenance and therapeutic responses. The cells also facilitate histone demethylase inhibitor screening and epigenetic target validation. For additional details, please contact Ascent Research.
