SETDB1, an H3K9-specific methyltransferase: An attractive epigenetic target to combat cancer

SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is an important epigenetic regulator catalyzing histone H3 lysine 9 (H3K9) methylation, specifically di-/tri-methylation. This regulation promotes gene silencing through heterochromatin formation. Aberrant SETDB1 expression, and its oncogenic role is evident in many cancers. Thus, SETDB1 is a valid target with novel therapeutic benefits. In this review, we explore the structural and biochemical features of SETDB1, its regulatory mechanisms, and its role in various cancers. We also discuss recent discoveries in small molecules targeting SETDB1 and provide suggestions for future research.