The BCL9 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of HAP1 cells with targeted disruption of the BCL9 gene. This heterogeneous pool of knockout cells is designed for functional studies of BCL9 in Wnt/??-catenin signaling without clonal isolation, preserving a spectrum of genomic edits. Researchers can use these cells to dissect BCL9-dependent transcription, oncogenesis, and signal transduction.
HAP1 is a near-haploid human male cell line derived from KBM-7 chronic myeloid leukemia cells. Its haploid karyotype simplifies genetic manipulation and minimizes functional redundancy, making it an ideal model for gene knockout and genetic screening. The cells grow adherently and maintain stable haploidy, providing a consistent system for loss-of-function studies in cancer biology and other fields.
BCL9 is a transcriptional coactivator that bridges ??-catenin (CTNNB1) and Pygopus (PYGO1/PYGO2) to assemble an active complex on Wnt-responsive promoters. Canonical Wnt activation by ligands like WNT3A via Frizzled and LRP5/6 leads to Dishevelled-mediated inhibition of the GSK3??/APC/AXIN destruction complex, stabilizing ??-catenin. Nuclear ??-catenin partners with TCF/LEF, and BCL9 is recruited, interacting with ??-catenin and Pygopus to facilitate chromatin remodeling and transcription of targets including MYC, CCND1, AXIN2, LEF1, TCF7, SP5, and NKD1. BCL9 also interacts with BCL9L, PARP1, and histone acetyltransferases. Its dysregulation is frequent in colorectal cancer, multiple myeloma, B-cell malignancies, hepatocellular carcinoma, and breast cancer, driving oncogenic transcription.
The BCL9 knockout in HAP1 cells offers a molecularly defined system to evaluate BCL9’s role in ??-catenin-dependent transcription. The near-haploid genome ensures efficient gene disruption, yielding a clear loss-of-function phenotype while avoiding polyploidy-related artifacts. HAP1 cells exhibit robust Wnt responsiveness, making them suitable for dissecting coactivator functions required for TCF/LEF-mediated gene expression and identifying BCL9-dependent gene signatures.
Research applications include Wnt pathway dissection, cancer biology, and drug target validation. Assays such as Western blotting, RT-qPCR, and TOPFlash/FOPFlash reporter assays quantify signaling outputs. Co-immunoprecipitation confirms loss of ??-catenin?CBCL9 interaction, and ChIP maps TCF/LEF occupancy. RNA-seq profiling reveals global transcriptional changes, while cell proliferation assays assess oncogenic potential. These polyclonal knockout cells are a versatile tool for Wnt research. For further information, please contact Ascent Research.
