The KDM5B Knockout T-47D Polyclonal Cells product comprises a population of CRISPR/Cas9-edited T-47D cells with targeted disruption of the KDM5B gene. This polyclonal knockout cell population is derived via CRISPR/Cas9-mediated gene editing and provides a heterogeneous pool of loss-of-function genotypes, reflecting the diversity of editing outcomes. The product serves as a versatile tool for studying KDM5B-dependent processes in a breast cancer context without the biases of clonal selection. Researchers can use these cells to interrogate the functional consequences of KDM5B ablation in downstream assays, leveraging the ensemble behavior of the polyclonal knockout population.
The parental cell line, T-47D, is a widely characterized model of estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER2-negative ductal carcinoma of the breast. Originally isolated from a pleural effusion, T-47D cells retain molecular features of luminal breast cancer, including dependency on estrogen signaling for growth and expression of hormone receptors. This line is frequently employed in investigations of endocrine therapy resistance, hormonal signaling crosstalk, and epithelial biology. The well-documented genomic and transcriptomic landscape of T-47D cells facilitates integration of CRISPR-edited derivatives into established experimental workflows.
KDM5B (also known as PLU-1/JARID1B) encodes a histone H3 lysine 4 trimethyl (H3K4me3) demethylase that functions as a transcriptional repressor. It associates with chromatin-modifying complexes containing HDAC1/2, SIN3A, and components of PRC2 to coordinate gene silencing via H3K4me3 demethylation at target promoters. KDM5B is transcriptionally regulated by MYC and estrogen receptor alpha (ER??) in breast cancer cells, and its activity is modulated by hypoxia-inducible factors (HIFs) and microRNAs such as miR-137. Downstream, KDM5B represses key genes, including the cyclin-dependent kinase inhibitor CDKN1A (p21), pro-apoptotic regulators, and differentiation markers, thereby promoting proliferation and stem-like properties. Its catalytic activity directly influences chromatin accessibility and transcription of estrogen-responsive genes and genes involved in epithelial-mesenchymal transition (EMT).
In T-47D cells, KDM5B contributes to the epigenetic repression of tumor-suppressive pathways and fine-tunes estrogen receptor signaling output. Knockout of KDM5B relieves H3K4me3 demethylation, leading to derepression of target genes such as p21 and pro-apoptotic factors, which may sensitize cells to tamoxifen. Consequently, the polyclonal knockout model enables dissection of H3K4me3 dynamics in hormone-dependent transcription, cell cycle progression, and drug response in an ER-positive breast cancer subtype.
Researchers can employ this polyclonal knockout product for comprehensive functional genomic studies, including RNA-seq and ChIP-seq analyses to map KDM5B-dependent transcriptomes and H3K4me3 redistribution. Cell-based assays such as proliferation, colony formation, and apoptosis assays, combined with tamoxifen sensitivity profiling, are ideal for evaluating therapeutic vulnerabilities. The model also facilitates screening of histone demethylase inhibitors and epistasis experiments to delineate KDM5B??s role in MYC-driven and PI3K/AKT signaling networks. For further details or technical support, please contact Ascent Research.
