KMT2C Knockout HAP1 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal cell population in which the KMT2C gene has been disrupted, generating a loss-of-function model for studying this critical histone methyltransferase. This product enables investigations into enhancer regulation, chromatin modification, and transcriptional control without the need for individual clone isolation, providing a heterogeneous knockout pool that approximates population-level gene disruption effects.
The host cell line, HAP1, is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia line. HAP1 cells exhibit an adherent, fibroblast-like morphology and retain a near-haploid karyotype, with the exception of disomy for chromosome 8. This haploid background facilitates unambiguous genotype-phenotype relationships, as only one allele is typically present, eliminating confounding effects from a second functional gene copy. Originally derived from a male patient, HAP1 is widely employed in genetic knockout studies due to its predictable editing outcomes and straightforward genetic manipulation.
KMT2C encodes a histone-lysine N-methyltransferase that functions as the catalytic subunit of the MLL3/MLL4 COMPASS-like complex, responsible for mono- and di-methylation of histone H3 at lysine 4 (H3K4me1/2) at enhancer regions. KMT2C activity is regulated by upstream signals including TP53, MYC, WNT signaling, retinoic acid receptor, and NOTCH. Upon activation, the complex interacts with core components ASH2L, RBBP5, WDR5, and DPY30, as well as cofactors NCOA6, PTIP, UTX, and PA1, to establish H3K4me1 marks. These marks facilitate enhancer activation and subsequent transcription of downstream targets such as CDKN1A, MYC, and HOX genes, linking KMT2C to diverse biological processes including cell growth, differentiation, and NOTCH-mediated signaling.
Disruption of KMT2C in the HAP1 model leads to a loss of H3K4me1 deposition at target enhancers, paralleling findings in cancer biology where KMT2C mutations are implicated in medulloblastoma, follicular lymphoma, B-cell lymphoma, colorectal cancer, endometrial cancer, and acute myeloid leukemia. The haploid nature of HAP1 cells amplifies the phenotypic consequences of KMT2C loss, revealing defects in enhancer?Cpromoter communication and transcriptional dysregulation that are masked in diploid systems. This makes the knockout cells a powerful tool for dissecting KMT2C-dependent enhancer networks and validating its role as a tumor suppressor or oncogenic factor in specific cellular contexts.
Researchers can employ KMT2C Knockout HAP1 Polyclonal Cells in a variety of applications including epigenetic regulation studies, enhancer biology investigations, and cancer research focused on transcriptional control mechanisms. Representative assays include ChIP-seq to map H3K4me1 occupancy and identify KMT2C-regulated enhancers, RNA-seq to profile global transcriptomic changes, western blotting and immunofluorescence to assess histone modification levels, and co-immunoprecipitation to examine MLL3/MLL4 complex integrity. These cells also serve for drug target validation, particularly for compounds targeting epigenetic modifiers. For additional product information, technical support, or custom project consultation, please contact Ascent Research.
