SETDB1

Gene Information

Official Symbol: SETDB1
Official Name: SET domain bifurcated histone lysine methyltransferase 1
Aliases and Previous Symbols: N/A
Entrez ID: 9869
UniProt: Q15047
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: 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 (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). 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). {ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:15327775, ECO:0000269|PubMed:17952062, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
MK-1775 0.32μM R02 exp75	-1.77
LY2090314 0.003μM R08 exp499	1.74
MLN-4924 0.2μM R00 exp21	1.77
MSC2530818 10μM R07 exp379	2.04
BVD-523 15μM R02 exp67	2.16
BML-284 0.09μM R08 exp460	2.41
Dorsomorphin 5μM R07 exp357	2.74
UMK57 1μM R01 exp59	3.14
2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312	3.48
UM131593 0.2μM R03 exp106	5.91

Gene	Correlation
ATF7IP	0.538
ID3	0.504
CBX3	0.495
TRIM28	0.479
ATAT1	0.471
ZNF592	0.463
BRPF1	0.458
EHMT2	0.458
ARL14EP	0.439
NSD1	0.434
MLLT1	0.429
AFF1	0.428
DDX5	0.418
CCDC101	0.408
TAF5L	0.406
AMBRA1	0.404

Global Fraction of Cell Lines Where Essential: 69/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	2/28
blood	9/28
bone	7/25
breast	1/33
central nervous system	1/56
cervix	0/4
colorectal	3/17
esophagus	4/13
fibroblast	0/1
gastric	1/15
kidney	1/21
liver	2/20
lung	5/75
lymphocyte	0/14
ovary	2/26
pancreas	2/24
peripheral nervous system	2/16
plasma cell	3/15
prostate	1/1
skin	0/24
soft tissue	0/7
thyroid	0/2
upper aerodigestive	4/22
urinary tract	3/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 1249
Expression level (log2 read counts): 6.48

Expression Distribution

MBD
SET
Pre-SET

histone methyltransferase activity (H3-K9 specific)
positive regulation of methylation-dependent chromatin silencing
regulation of methylation-dependent chromatin silencing
positive regulation of chromatin silencing
negative regulation of single stranded viral RNA replication via double stranded DNA intermediate
histone H3-K9 methylation
regulation of single stranded viral RNA replication via double stranded DNA intermediate
histone H3-K9 modification
histone-lysine N-methyltransferase activity
regulation of chromatin silencing
promoter-specific chromatin binding
negative regulation of viral genome replication
histone lysine methylation
negative regulation of viral life cycle
response to vitamin
peptidyl-lysine methylation
histone methylation
regulation of viral genome replication
negative regulation of viral process
positive regulation of chromatin organization
chromosome
response to ethanol
regulation of gene silencing
protein alkylation
protein methylation
regulation of viral life cycle
positive regulation of chromosome organization
regulation of chromatin organization
regulation of viral process
response to nutrient
negative regulation of multi-organism process
regulation of symbiosis, encompassing mutualism through parasitism
response to alcohol
Ras protein signal transduction
macromolecule methylation
response to antibiotic
methylation
peptidyl-lysine modification
small GTPase mediated signal transduction
regulation of chromosome organization