The ATAD2 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the ATAD2 gene in a near-haploid host background. This product provides a loss-of-function model generated through CRISPR/Cas9-mediated gene disruption, preserving genetic heterogeneity while allowing robust functional studies. ATAD2 is an oncogenic chromatin regulator and transcriptional coactivator frequently overexpressed in diverse cancers, and its knockout is valuable for dissecting tumorigenic mechanisms. The polyclonal format enables pooled analysis of knockout effects without clonal selection, suitable for unbiased screening and validation experiments.
HAP1 cells, the host line, are derived from the KBM-7 chronic myeloid leukemia (CML) cell line and retain a near-haploid, adherent fibroblast-like morphology. Established from a male patient, this background offers simplified genetic analysis due to its haploid karyotype while maintaining key features of leukemic signaling. HAP1 cells are widely used for haploid genetic screens and target dependency studies, making them an ideal platform for investigating oncogene function and therapeutic vulnerabilities in a CML context.
ATAD2 functions as a coactivator for oncogenic transcription factors MYC and E2F1, and it integrates signals from the androgen receptor and PI3K/AKT pathways. ATAD2 directly interacts with MYC, E2F1, androgen receptor, and SSRP1 of the FACT complex, binding acetylated histones H3 and H4 via its bromodomain and ATPase domains to remodel chromatin. This activity drives transcription of cell cycle and DNA replication regulators including CCNE1, CCNA2, the MCM2-7 helicase complex, CDK1, and CDC6, promoting S-phase entry and genomic instability. Key pathway components linking ATAD2 to downstream effects include cyclins, CDKs, MCM proteins, and histone acetyltransferases such as p300/CBP, positioning ATAD2 at a critical node in proliferation control.
In the HAP1 leukemic background, ATAD2 disruption permits detailed investigation of its role in maintaining proliferation and survival of cancer cells. The near-haploid genome enhances genotype-phenotype clarity, allowing dissection of ATAD2-dependent signaling required for leukemic growth. Given ATAD2’s involvement in breast, prostate, lung, hepatocellular carcinoma, and acute myeloid leukemia, this model is a versatile tool for studying oncogene addiction across cancer types and for exploring synthetic lethality in the context of chromatin and cell cycle dysregulation.
Typical research applications include Western blotting, RT-qPCR, and RNA-seq to confirm ATAD2 loss and characterize global transcriptional changes; ChIP-qPCR to assess ATAD2 and histone acetylation at target gene promoters; cell proliferation and cell cycle analysis via flow cytometry; co-immunoprecipitation to validate protein interactions; and drug sensitivity screening with bromodomain inhibitors. These polyclonal ATAD2 knockout cells thus support cancer biology, epigenetic regulation, and target validation studies. For additional technical information, please contact Ascent Research.
