SETDB1 Protein, Human (sf9, GST)

ESET is a histone methyltransferase that specifically trimethylates histone H3 at lysine 9 (H3K9me3), a mark for epigenetic transcriptional repression via recruitment of HP1 proteins (e.g., CBX1, CBX3, and/or CBX5). It primarily functions in euchromatin, playing a central role in silencing euchromatic genes, and coordinates with DNA methylation (e.g., in HUSH-mediated heterochromatin formation). ESET forms a complex with MBD1 and ATF7IP to repress transcription by coupling DNA methylation and H3K9me3, with its activity heritably maintained by CAF-1 during DNA replication. TRIM28/TIF1B recruits ESET to H3, facilitated by KRAB zinc-finger proteins. In colorectal cancer cells, ESET likely mediates KRAS-activated promoter hypermethylation and silencing of tumor suppressor genes (TSGs). It also maintains repressive gene states in undifferentiated embryonic stem cells (ESCs) and, with TRIM28, silences endogenous/retroviral elements independently of DNA methylation (by similar). The ESET-TRIM28-ZNF274 complex may guide ATRX to zinc-finger gene exons to safeguard H3K9me3 at transcriptionally active regions.