The KAT7 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population derived from the near-haploid HAP1 cell line, designed to disrupt the KAT7 gene. This pooled loss-of-function model enables robust study of KAT7-dependent processes in a genetically simplified background, making it suitable for functional genomics, epigenetics, and drug target validation.
HAP1 is a male, near-haploid, fibroblast-like cell line derived from the KBM-7 chronic myeloid leukemia line. Its haploid karyotype (except for disomic chromosome 8) allows complete gene inactivation with a single targeting event, rendering it a powerful system for knockout screens and mechanistic studies of gene function. The cells proliferate rapidly and are amenable to standard genetic manipulation and assay protocols.
KAT7 encodes a histone acetyltransferase that serves as the catalytic subunit of the HBO1 complex, which also contains BRPF1/2/3, JADE1/2/3, ING4/5, and MEAF6. This complex acetylates histone H4 at lysines 5, 8, and 12, promoting chromatin decompaction and the loading of replication licensing factors ORC1, Cdt1, and the MCM2-7 helicase. KAT7 activity is regulated by CDK1/Cyclin B1, Cdt1, the APC/C ubiquitin ligase, ATM/ATR kinases, and E2F transcription factors, and it converges with Wnt/??-catenin signaling through interaction with CTNNB1 and TCF7L2. KAT7 also acetylates p53 at K120 and K382, modulating its transcriptional function.
In the near-haploid HAP1 background, KAT7 disruption produces a clear loss-of-function model for investigating how histone H4 acetylation controls DNA replication licensing, cell cycle progression, and chromatin dynamics. This model is particularly relevant for cancers where KAT7 is implicated??such as acute myeloid leukemia, breast cancer, and hepatocellular carcinoma??and enables the study of oncogenic transcriptional dependencies and synthetic lethal interactions within the HBO1 network.
Key applications include ChIP-qPCR for assessing H4 acetylation at origins, DNA fiber assays for replication fork analysis, EdU incorporation with flow cytometry for cell cycle analysis, and co-immunoprecipitation to probe HBO1 complex composition. Proliferation and viability can be measured via colony formation and MTT assays. These cells also facilitate genome-wide CRISPR screens and drug sensitivity profiling. For further support, please contact Ascent Research.