DISEASES

Disease-gene associations mined from literature

Literature on SETDB1

SETDB1 [ENSP00000271640]

Histone-lysine N-methyltransferase SETDB1; 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 . 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 . 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 . Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) . 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 . 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 . ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:15327775, ECO:0000269|PubMed:17952062, ECO:0000269|PubMed:24623306,

Synonyms:  SETDB1,  SETDB1p,  hSETDB1,  B0QZE6,  E9PAP1 ...

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