The BRMS1L Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population with targeted disruption of the BRMS1L gene in the HAP1 human near-haploid cell line. This polyclonal format provides a genetically diverse pool of knockout cells, minimizing clonal artifacts and ensuring reproducible functional studies of BRMS1L-dependent processes.
HAP1 is a fibroblast-like, adherent cell line derived from the KBM-7 chronic myeloid leukemia line. Its near-haploid karyotype (except for disomy of chromosome 8) permits efficient CRISPR-based gene knockout because single-allele disruption eliminates gene function. This feature, combined with retention of cancer-relevant signaling pathways, makes HAP1 an optimal host for rapid functional genomics and genetic screening applications.
BRMS1L functions as a metastasis suppressor by serving as a core component of the SIN3A-HDAC transcriptional repressor complex. The complex, containing SIN3A, HDAC1, HDAC2, SAP18, and ARID4B, represses genes that drive epithelial-mesenchymal transition (EMT) and cell migration, notably VIM, CDH2, MMP2, and MMP9, as well as NF-??B targets such as CCND1 and BIRC5. BRMS1L expression is regulated by upstream signals including TGF-??1 and the transcription factors ZEB1 and SNAI1, and is downregulated by miRNAs miR-106b and miR-21. Disruption of BRMS1L leads to derepression of these targets, promoting a pro-migratory and invasive phenotype.
In HAP1 cells, BRMS1L knockout is expected to relieve transcriptional repression of mesenchymal and migratory genes, enhancing cellular motility and invasion. The haploid background amplifies the knockout effect, yielding a clean model to study the SIN3A complex’s role in metastasis suppression and its interplay with the TGF-??/Smad and NF-??B pathways. This system simplifies the investigation of BRMS1L-mediated epigenetic regulation without the complexity of a diploid genome.
Research applications include functional dissection of metastasis suppressor mechanisms, screening for EMT modulators, drug target validation in cancer, and analysis of SIN3A-HDAC complex function. Representative assays with these cells encompass western blotting for EMT markers (E-cadherin, vimentin), transwell migration/invasion assays, ChIP-qPCR of target promoters, NF-??B luciferase reporter assays, co-immunoprecipitation of the SIN3A complex, and RNA-seq transcriptome profiling. For additional inquiries, contact Ascent Research.
