The KDM6B Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the KDM6B gene in the HAP1 human cell line. This loss-of-function model enables researchers to investigate the functional consequences of KDM6B depletion, including its role as a histone demethylase that removes the repressive H3K27me3 mark. By generating a heterogeneous pool of knockout cells, this product provides a versatile tool for studying gene function without requiring clonal isolation.
HAP1 is a near-haploid human cell line derived from the chronic myeloid leukemia (CML) cell line KBM-7. Its near-haploid karyotype, with a single set of chromosomes over most of its genome, facilitates gene knockout studies by eliminating the need to target multiple alleles. This feature makes HAP1 cells particularly valuable for genetic screens and functional genomics, as loss-of-function mutations can be rapidly assessed without confounding contributions from a second allele.
KDM6B encodes a H3K27me3-specific demethylase that promotes gene activation by erasing repressive methyl marks. It is regulated by upstream signals including NF-??B, TGF-??, hypoxia, retinoic acid, STAT3, and JNK. Upon activation, KDM6B removes H3K27me3 at target loci, enabling transcription of key downstream genes such as HOX clusters, CDKN2A (p16INK4A and p14ARF), BMP2, DKK1, and pro-inflammatory cytokines like IL-6 and TNF. KDM6B interacts with chromatin-modifying complexes, including MLL3/4, UTX, ASXL1, BRG1, CDK9, and P-TEFb, and functions in pathways like NF-??B (p65, IKK??), TGF-?? (SMAD2/3, SMAD4), Notch (NICD, RBPJ), and retinoic acid (RARs). This network positions KDM6B at the intersection of inflammation, development, and tumor suppression.
In the HAP1 background, KDM6B knockout provides a clean genetic system to dissect its dual roles in promoting gene expression for differentiation and inflammation, while also acting as a tumor suppressor in certain contexts. The near-haploid nature ensures efficient knockout and reduces genetic redundancy, making this model ideal for studying signaling crosstalk and epigenetic regulation in a simplified genomic environment. Researchers can explore how loss of KDM6B alters NF-??B- or TGF-??-driven transcriptional programs, and assess its impact on proliferation, apoptosis, and drug resistance.
This polyclonal knockout cell product supports a wide range of research applications, including epigenetic drug screening, functional genomics, and investigations into hematopoietic malignancies, solid tumors, inflammatory diseases, and neurodevelopmental disorders. Typical assays performed on these cells include Western blot analysis of KDM6B and global H3K27me3 levels, RT-qPCR for downstream target expression, RNA-seq for transcriptome-wide profiling, ChIP-qPCR to assess H3K27me3 occupancy, flow cytometry for phenotypic analysis, and reporter assays monitoring NF-??B or TGF-?? activity. Proliferation, apoptosis, and drug sensitivity studies further expand its utility in cancer and inflammation research. For additional information, please contact Ascent Research.
