The BRD3 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population targeting the BRD3 gene in the near-haploid human HAP1 cell line. This product provides a loss-of-function model for exploring BRD3-mediated transcriptional regulation and epigenetic signaling. The polyclonal format avoids clonal selection, representing a pooled knockout cell population suitable for unbiased functional screening and mechanistic studies. It is designed for advanced research into BET bromodomain proteins and their roles in oncogenesis.
HAP1 cells are a near-haploid derivative of the KBM-7 chronic myeloid leukemia line, providing a simplified genetic background for gene knockout studies. The haploid genome reduces gene dosage complexity, facilitating efficient CRISPR/Cas9-mediated editing of a single allele. These cells maintain key leukemia-associated signaling dependencies, making them a relevant model for studying cancer-relevant genes such as BRD3. The BRD3 knockout polyclonal cell pool capitalizes on these features to offer a versatile platform for functional genomics.
BRD3 functions as a BET family bromodomain protein that binds acetylated lysine residues on histones H3 and H4, localizing to active enhancers and super-enhancers to drive transcription. It is activated by histone acetyltransferases p300/CBP and phosphorylated by CK2, and it interacts with BRD2, BRD4, Mediator complex, and P-TEFb to promote RNA polymerase II elongation. BRD3 directly regulates key oncogenes including MYC, BCL2, CDK6, and CCND1, linking epigenetic marks to cell cycle progression and survival. CRISPR-mediated gene disruption ablates this regulatory network, leading to reduced oncogene expression and impaired cancer cell growth.
Within the HAP1 chronic myeloid leukemia context, BRD3 knockout models BET protein dependency in hematological malignancies. Loss of BRD3 disrupts super-enhancer-mediated oncogene transcription, sensitizing cells to apoptosis and cell cycle arrest. This polyclonal knockout population captures a range of phenotypic responses, suitable for pharmacological modulation with BET inhibitors and for studying NUT midline carcinoma, AML, and other BET-driven cancers. It also enables exploration of epigenetic crosstalk and synthetic lethal interactions in leukemia.
Research applications encompass BET bromodomain inhibitor target validation using dose-response assays, transcriptome-wide profiling via RNA-seq, and chromatin immunoprecipitation (ChIP)-qPCR to assess histone acetylation at BRD3 target loci. Functional endpoints include MTT proliferation and Annexin V apoptosis assays. The polyclonal population is also suitable for high-throughput epigenetic drug screens and genetic interaction mapping. For technical support, please contact Ascent Research.
