The EHMT2 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population designed for targeted gene disruption of EHMT2 in the 786-O human clear cell renal cell carcinoma (ccRCC) cell line. The knockout is achieved through CRISPR/Cas9-mediated gene disruption, generating a loss-of-function model suitable for epigenetic and cancer studies. This product provides a genetically heterogeneous knockout model, enabling loss-of-function studies with reduced clonal artifacts.
The 786-O host cell line is a human epithelial cancer cell line originating from a primary clear cell renal cell carcinoma. It carries a loss-of-function mutation in the VHL tumor suppressor gene, resulting in constitutive stabilization of hypoxia-inducible factors (HIFs) and activation of hypoxic transcriptional programs. This genetic background makes 786-O a standard model for studying ccRCC pathogenesis, including hypoxia-driven proliferation and drug resistance.
EHMT2 (G9a) catalyzes mono- and dimethylation of H3K9, leading to transcriptional repression through HP1 recruitment. It functions in complexes with EHMT1 and WIZ, and interacts with transcriptional repressors REST and SNAIL. EHMT2 is regulated by upstream signals such as E2F1, MYC, RAS-ERK, and PI3K-AKT pathways, and responds to DNA damage. Downstream, it silences tumor suppressors including TP53, CDKN1A, CDH1, and RB1, thereby promoting cell cycle progression, survival, and EMT. It also recruits DNMT1 to target loci, coupling histone and DNA methylation.
In the VHL-mutant 786-O context, EHMT2-mediated silencing cooperates with HIF-driven transcription, repressing genes such as E-cadherin and p53 to enhance proliferation, invasion, and EMT. Disruption of EHMT2 in these cells allows dissection of the epigenetic silencing axis independent of hypoxia signaling, making it a valuable model for investigating H3K9 methylation in renal cancer and its crosstalk with p53 and WNT pathways. This model is particularly useful for studying the role of EHMT2 in ccRCC tumor progression and for evaluating EHMT2-targeted therapies.
This polyclonal knockout population supports diverse applications: proliferation, migration, and apoptosis assays; ChIP-qPCR and RNA-seq for epigenetic and transcriptomic profiling; drug target validation and EHMT2 inhibitor screening; co-immunoprecipitation to analyze EHMT2-containing complexes; and hypoxia response studies. For further technical details, please contact Ascent Research.
