The KAT6A Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the KAT6A gene in the near-haploid human HAP1 cell line. This polyclonal pool provides a heterogeneous loss-of-function model for studying KAT6A-dependent cellular processes. The CRISPR/Cas9-mediated gene disruption introduces targeted alterations within the KAT6A locus, generating a mixed cell population with varied editing outcomes that collectively abolish functional KAT6A expression. This product is an ideal tool for functional genomics studies, drug target validation, and chromatin biology research requiring a robust knockout background.
HAP1 is a near-haploid human myeloid leukemia cell line derived from the KBM-7 chronic myeloid leukemia cell line. It exhibits a fibroblast-like, adherent morphology and a stable karyotype with less than 10% diploid cells. HAP1 cells retain the BCR-ABL fusion characteristic of chronic myeloid leukemia, providing a unique genetic background for studying gene function. The near-haploid nature of HAP1 facilitates efficient CRISPR screening and simplifies functional genomic analyses compared to diploid models, making it a powerful platform for knockout studies.
KAT6A (lysine acetyltransferase 6A) is a histone acetyltransferase that functions as a transcriptional coactivator by acetylating lysine residues on histones H3 and H4, thereby promoting an open chromatin state. It forms complexes with ING5, BRPF1, and EAF6, and interacts with EP300/CREBBP to mediate acetylation-dependent transcriptional activation. KAT6A is activated by ATM kinase in the DNA damage response, regulated by Notch and retinoic acid receptor signaling, and coactivates p53-dependent transcription. Downstream, KAT6A targets include HOXA cluster genes, p53 target genes such as CDKN1A and BAX, and RUNX1 target genes, all of which are critical for hematopoietic stem cell self-renewal and differentiation.
In the HAP1 cell line, KAT6A knockout provides a valuable model for dissecting the role of histone acetylation in leukemia biology and hematopoiesis. As HAP1 cells harbor the BCR-ABL fusion, the knockout enables investigation of KAT6A contributions to oncogenic signaling and p53 pathway regulation in a haploid genetic context. The polyclonal population captures a spectrum of mutations, allowing assessment of diverse loss-of-function effects on proliferation, apoptosis, and drug sensitivity. This model is particularly suited for studying transcriptional regulation by KAT6A-containing complexes and their impact on target gene expression networks involved in AML.
Typical applications include functional genomic screens, chromatin immunoprecipitation to assess histone H3/H4 acetylation changes, and transcriptional profiling by RNA-seq to identify KAT6A-dependent genes. Researchers can perform RT-qPCR for target genes such as HOXA9 and CDKN1A, western blotting to confirm KAT6A depletion, and co-immunoprecipitation to study complex integrity. Downstream phenotypic assays like proliferation, colony formation, and drug sensitivity testing enable evaluation of KAT6A as a therapeutic target in leukemia. For more information, please contact Ascent Research.
