Figure 1.

SETDB1 enables AML cells to evade innate immune sensing of retrotransposons. Cancer cells elevate their levels of SETDB1, which promotes the formation of H3K9me3-based heterochromatin at retrotransposons. This in turn prevents transcription of retrotransposon-derived dsRNA and its downstream recognition by cytosolic RNA sensors. Genetic ablation of SETDB1 leads to a type I IFN response, the subsequent activation of ISGs, and apoptosis. LINE1, long interspersed nuclear element 1; sgRNA, single-guide RNA.