FEATURES

FAMILY

DESCRIPTION

Also known as SETB1_HUMAN, SETDB1, ESET, KIAA0067, KMT1E. 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 (PubMed:12869583). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:27732843, PubMed:14536086). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086, ). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). Part of a complex containing at least CDYL, REST, WIZ, SETDB1, EHMT1 and EHMT2 (PubMed:19061646). Forms a complex with ATRX, TRIM28 and ZNF274 (PubMed:27029610). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306). Interacts with TRIM28/TIF1B (PubMed:11959841). Interacts with ATF7IP and ATF7IP2; the interaction with ATF7IP protects SETDB1 from proteasomal degradation and is required to stimulate histone methyltransferase activity and facilitate the conversion of dimethylated to trimethylated H3 'Lys-9' (PubMed:14536086, PubMed:15691849). Interacts with CBX1 and CBX5 (PubMed:15899859). Interacts with DNMT3A and DNMT3B (PubMed:16682412). Interacts with SUMO2. Interacts with MPHOSPH8 (PubMed:20871592). Interacts with ERG (By similarity). Interacts with HDAC1, HDAC2, SIN3A and SIN3B (By similarity). Interacts with ATRX. Interacts with RESF1 (By similarity). Interacts with ZNF638 (PubMed:30487602). Interacts with TASOR (By similarity). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553).

EXTERNAL LINKS

SETDB1

Histone-lysine N-methyltransferase SETDB1

SETDB1

Molecular Synopsis