The SETD2 Knockout HMC3 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from the HMC3 human microglial cell line. This product introduces a targeted disruption of the SETD2 gene, which encodes a histone methyltransferase responsible for catalyzing trimethylation of histone H3 at lysine 36 (H3K36me3). The knockout model provides a valuable tool for studying loss-of-function effects in a biologically relevant microglial context, without imposing specific assumptions about editing mechanisms or clonality. Users can employ this cell line to dissect SETD2-dependent epigenetic regulation and DNA repair processes within the central nervous system’s innate immune cells.
HMC3 cells are a human microglial cell line derived from fetal brain tissue, widely used for neuroinflammation research. These cells perform immune surveillance, phagocytosis, and cytokine production in the CNS, making them essential for investigating microglial function in health and disease. HMC3 cells provide a reproducible human model that retains key characteristics of primary microglia, offering a scalable platform for studying cellular stress responses and neuron-glia interactions.
SETD2 is the primary methyltransferase responsible for H3K36me3, a modification linked to transcriptional elongation, pre-mRNA splicing, and DNA mismatch repair. The enzyme associates with RNA polymerase II (POLR2A) and interacts with hnRNPs to coordinate co-transcriptional events. Upstream regulators include p53 and hypoxia, while downstream, H3K36me3 marks recruit the MutS?? complex (MSH2-MSH6) and influence p53 target gene expression. SETD2??s role in splicing regulation further highlights its function in maintaining transcriptome integrity. Disruption of SETD2 ablates H3K36me3 deposition, compromising DNA damage signaling and altering gene expression programs essential for tumor suppression and genomic stability.
In microglia, SETD2-mediated epigenetic control likely governs genes involved in immune activation, phagocytosis, and cytokine secretion. Loss of SETD2 may dysregulate neuroinflammatory pathways and impair DNA repair after oxidative or genotoxic insults, which microglia frequently encounter in the CNS environment. This knockout cell line therefore permits detailed study of how histone methylation shapes microglial responses and contributes to neurodevelopmental disorders or cancer-related neuroinflammatory conditions.
This model is suitable for ChIP-qPCR analyses of H3K36me3, western blotting for SETD2, and RNA sequencing to capture transcriptomic alterations. DNA damage assays including the comet assay can evaluate repair kinetics, while cell viability assays measure stress sensitivity. Applications span cancer epigenetics, DNA repair, neuroinflammation, and microglial biology. For further technical information or ordering, please contact Ascent Research.
