The KAT6B Knockout Jurkat Polyclonal Cells constitute a polyclonal population of CRISPR/Cas9-edited Jurkat T-lymphoblasts with disrupted KAT6B expression. This heterogeneous pool of loss-of-function cells minimizes clonal artifacts and provides a robust system for studying the impact of KAT6B depletion on epigenetic regulation and leukemogenesis.
Jurkat E6-1 is an immortalized human T-cell line derived from acute T-cell leukemia, widely used to investigate T-cell receptor signaling, apoptosis, and leukemic transformation. Its activated T-lymphocyte phenotype makes it an ideal host for examining chromatin modifiers involved in lymphocyte biology.
KAT6B (MYST4/MORF) is a histone acetyltransferase that acetylates histones H3 and H4, serving as a transcriptional coactivator for RUNX2 and Notch intracellular domain (NICD). It forms complexes with BRD1, ING5, EAF6, HBO1, and hMOF, and is regulated by NICD, RUNX2, c-Myb, SIRT1, and retinoic acid receptors. KAT6B acetylates p53 and other non-histone substrates, influencing protein stability and function. Downstream genomic targets include HOXA1, HOXB1, RUNX2-regulated genes, and p53-dependent loci. In the Notch pathway, NICD partners with RBPJ and MAML1 to recruit KAT6B, which then acetylates histones at HES1 and HOXA9 promoters, driving transcription. CRISPR/Cas9-mediated disruption eliminates KAT6B acetyltransferase activity, leading to reduced histone acetylation and dysregulation of gene networks essential for proliferation, differentiation, and leukemogenesis.
In Jurkat T-cells, KAT6B likely sustains oncogenic transcription by coactivating Notch and RUNX2 targets. Its knockout is predicted to impair proliferation and survival, offering a model to interrogate epigenetic dependencies in T-ALL. The polyclonal nature ensures representation of heterogeneous editing events, reducing clonal bias and reflecting biological variability.
These polyclonal knockout cells are suitable for mechanistic studies of chromatin regulation in leukemia, high-throughput HAT inhibitor screening, and disease modeling of KAT6B-associated syndromes (genitopatellar, Say-Barber-Biesecker-Young-Simpson). Assays such as ChIP-qPCR for histone acetylation marks, RNA-seq, western blotting, HAT activity measurements, flow cytometry, and Notch reporter assays are directly compatible. Additionally, these cells can be used to investigate the role of KAT6B in T-cell receptor signaling and apoptosis, as well as to validate potential therapeutic targets downstream of epigenetic coactivators in leukemia. For more information, please contact Ascent Research.
