Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins.
Widely expressed. High expression in testis.
Belongs to the histone-lysine methyltransferase family. Suvar3-9 subfamily. Contains 1 MBD (methyl-CpG-binding) domain. Contains 1 post-SET domain. Contains 1 pre-SET domain. Contains 1 SET domain. Contains 2 Tudor domains.
The pre-SET, SET and post-SET domains are all required for methyltransferase activity. The 347-amino-acid insertion in the SET domain has no effect on the catalytic activity. Isoform 2 lacks all domains required for histone methyltransferase activity.
Nucleus. Chromosome. Associated with non-pericentromeric regions of chromatin. Excluded from nucleoli and islands of condensed chromatin.
Overlay histogram showing Ramos cells stained with ab107225 (red line). The cells were fixed with 80% methanol (5 min) and then permeabilized with 0.1% PBS-Tween for 20 min. The cells were then incubated in 1x PBS / 10% normal goat serum / 0.3M glycine to block non-specific protein-protein interactions followed by the antibody (ab107225, 1/100 dilution) for 30 min at 22ºC. The secondary antibody used was DyLight® 488 goat anti-mouse IgG (H+L) (ab96879) at 1/500 dilution for 30 min at 22ºC. Isotype control antibody (black line) was mouse IgG1 [ICIGG1] (ab91353, 2µg/1x106 cells) used under the same conditions. Acquisition of >5,000 events was performed. This antibody gave a positive signal in Ramos cells fixed with 4% paraformaldehyde (10 min)/permeabilized with 0.1% PBS-Tween for 20 min used under the same conditions.
Ropa J et al. PAF1 complex interactions with SETDB1 mediate promoter H3K9 methylation and transcriptional repression of Hoxa9 and Meis1 in acute myeloid leukemia. Oncotarget9:22123-22136 (2018).
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