The HDAC7 Knockout HAP1 Polyclonal Cells are a pool of CRISPR/Cas9-edited HAP1 cells with targeted disruption of the HDAC7 gene, creating a loss-of-function model for functional studies. This polyclonal population offers a heterogeneous editing background, minimizing clone-specific artifacts and enabling robust evaluation of HDAC7-dependent phenotypes in a near-haploid context. The knockout abolishes HDAC7 protein expression, facilitating investigation of its roles in transcriptional regulation and signal transduction.
The parental HAP1 line is a near-haploid human chronic myeloid leukemia (CML) derivative of KBM-7, with adherent growth and a single copy of most chromosomes. This haploid karyotype simplifies genetic manipulation and phenotype assessment, as gene disruption often yields complete loss-of-function. HAP1 cells are widely used in functional genomics, including genome-wide CRISPR screens, due to their ease of culture and well-characterized proteome, making them an ideal host for cancer-relevant gene function studies.
HDAC7 is a class IIa histone deacetylase and transcriptional corepressor that deacetylates histones and interacts with MEF2 transcription factors (MEF2A, C, D). Its activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling: upstream kinases PKD1, CaMK, and AMPK phosphorylate HDAC7, promoting 14-3-3 binding and nuclear export to relieve repression. HDAC7 integrates signals from VEGFR2, TNF-alpha, and TGF-beta to modulate downstream targets including MMP-10, PDGF-B, and EDN1. It forms complexes with HDAC3 and the NCoR/SMRT corepressor, and interacts with HIF1A and estrogen receptor alpha. This places HDAC7 at the intersection of VEGF, TGF-??, Wnt, mTOR, and immune pathways, governing vascular development, immune homeostasis, and differentiation.
In HAP1 leukemia cells, HDAC7 disruption provides a model to study its roles in oncogenic signaling, apoptosis, and drug sensitivity. Derived from a CML background, these cells retain hematopoietic malignancy features, including reliance on specific transcriptional programs. HDAC7 loss enables dissection of MEF2 target gene regulation, influencing cell cycle and sensitivity to tyrosine kinase inhibitors or chemotherapeutics. Additionally, HDAC7??s involvement in VEGF signaling and immune modulation allows exploration of epigenetic crosstalk with the tumor microenvironment and potential therapeutic synergies with targeted agents.
Research applications include functional genomics screens under selective pressure, and mechanistic studies using ChIP-qPCR, co-immunoprecipitation, and reporter assays to map HDAC7 interactomes and target networks. High-content readouts like RNA-seq and phospho-signaling analysis enable transcriptome and pathway dissection, while apoptosis and drug sensitivity assays assess therapeutic vulnerabilities. Immunofluorescence and flow cytometry support spatial and quantitative protein analysis. These cells are a versatile tool for vascular biology, leukemia, and autoimmune disease research. For further information, please contact Ascent Research.
