Protein: Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (SET domain bifurcated 1) (O88974)
Organism: Mus musculus (Mouse)
Function: 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. 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 (By similarity). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. 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 (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:29728365}. Chromosome {ECO:0000269|PubMed:29728365}. Note=Associated with non-pericentromeric regions of chromatin. {ECO:0000250|UniProtKB:Q15047}.
Interaction partners:
- Transcription intermediary factor 1-beta
- DNA
- Activating transcription factor 7-interacting protein 1
- Chromobox protein homolog 5
- Histone deacetylase 1
- DNA
- Histone-lysine N-methyltransferase SUV39H1
- DNA
- Histone-lysine N-methyltransferase EHMT2
- ARL14 effector protein
Sequence:
MSSLPGCMSLAAAPAAADSAEIAELQQAVVEELGISMEELRQYIDEELEKMDCIQQRKKQLAELETWVLQKESEVAYVDRLFDDASREVTNCESLVKDFYSKLGLQYHDSSSEDEASRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDLHKGTLGQVSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGLGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLFVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPLKKTWEDIEDSSCRDFIEEYITAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASAMEKKQGGQLRTRPNMGAVRSKGPVVQYTQDLTGTGIQFKPMEPLQPIAPPAPLPIPPLSPQAADTDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSSTLSENVSAGKLGINQTYRSPLASVTSTPASAAPPVPPVPPGPPTPPGPPAPPGPLAPPAFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRIRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPFKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQVNPNSGYQYKRLEECLPTGVYECNKRCNCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDVPTSSDSSGVDMKDQEDGNSGSEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENELSEMTSKDSRPPDLGPPHVPIPSSVSVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSRSSFKTSEGGDGRAGGGRGEAERASTSGLSFKDEGDNKQPKKEDPENRNKMPVVTEGSQNHGHNPPMKSEGLRRPASKMSVLQSQRVVTSTQSNPDDILTLSSSTESEGESGTSRKPTAGHTSATAVDSDDIQTISSGSDGDDFEDKKNLSGPTKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL