EC Number   |
General Information |
Reference  |
|---|
   2.1.1.366 | physiological function |
SETDB1 is a major enzyme for H3K9 histone methylation in heterochromatin |
759155 |
| 2.1.1.366 | physiological function |
H3K9 methylation reader M-phase phosphoprotein 8 (MPP8) interacts physically and functionally with SETDB1 in embryonic stem cells. MPP8 and SETDB1 coregulate a significant number of common genomic targets, especially the DNA satellite repeats |
759299 |
| 2.1.1.366 | physiological function |
histone H3K9 methyltransferases G9a/KMT1C, GLP/KMT1D, SETDB1/KMT1E, and Suv39h1/KMT1A, coexist in the same megacomplex. In Suv39h or G9a null cells, the remaining histone H3K9 methyltransferases are destabilized at the protein level, indicating. The four enzymes are recruited to major satellite repeats, a known Suv39h1 genomic target, but also to multiple G9a target genes. The four H3K9 histone H3K9 methyltransferases display a functional cooperation in the regulation of known G9a target genes |
759762 |
| 2.1.1.366 | physiological function |
Setdb1 has a constant role in endogenous retrovirus silencing. Distinctive sets of endogenous retroviruses are reactivated in different types of Setdb1-deficient somatic cells, including the VL30-class of endogenous retroviruses in mouse embryonic fibroblasts. A viral defense response is induced in immortalized Setdb1 knock-out embryonic fibroblasts |
759835 |
| 2.1.1.366 | physiological function |
the SETDB1 repressor complex, which involves multiple KRAB zinc finger proteins, shields neuronal genomes from excess CTCF binding and is critically required for structural maintenance of cPcdh topologically associated domain. Neuronal ablation of Setdb1 leads to locus-specific disintegration of megabase-scale chromosomal conformations. The cPcdh topologically associated domain in neurons from mutant mice shows abnormal accumulation of the transcriptional regulator and three-dimensional genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression. Genes encoding stochastically expressed protocadherins are transcribed by increased numbers of cortical neurons. SETDB1-dependent loop formations bypass 0.2-1 Mb of linear genome and radiate from the cPcdh topologically associated domain fringes toward cis-regulatory sequences within the cPcdh locus |
759838 |
| 2.1.1.366 | physiological function |
deletion of the catalytic domain of either histone methyltransferases EHMT2 or SETDB1 in growing oocytes leads to significant reduction of global H3K9me2 or H3K9me3 levels, respectively, in the maternal pronucleus. The asymmetry of global 5-methylcytosine (5mC) oxidation is significantly reduced in the zygotes that carry maternal mutation of either the Ehmt2 or Setdb1 genes. The levels of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine increase, and 5mC levels decrease in the mutant maternal pronuclei. H3K9me3-rich rings around the nucleolar-like bodies retain 5mC in the maternal mutant zygotes. The maternal pronuclei expand in size in the mutant zygotes and contain a significantly increased number of nucleolar-like bodies compared with normal zygotes |
760074 |
| 2.1.1.366 | physiological function |
SETDB1 regulates the development of cortical Htr3a-positive interneurons and mood behaviors |
776709 |
| 2.1.1.366 | drug target |
downregulating SETDB1 is an attractive therapeutic option in AKT-driven cancer and for enhancing the immunotherapeutic response |
777166 |
| 2.1.1.366 | malfunction |
aberrant SETDB1 expression, and its oncogenic role is evident in many cancers. Amplified SETDB1 is associated with enhanced tumorigenesis and poor prognosis in a wide variety of cancers. This increased oncogenic effect is probably due to a SETDB1 methylation-associated suppressive effect on various tumor suppressors, AKT hyperactivation, and increased mutant p53 stability. SETDB1 overexpression shows a significant negative correlation with immunomodulatory outcomes through tumor immune evasion and IFN-I pathway repression |
777166 |
| 2.1.1.366 | physiological function |
the enzyme is involved in various regulatory processes such as cell proliferation, progression, migration, survival, and apoptosis. The enzyme is an important epigenetic regulator catalyzing histone H3 lysine 9 (H3K9) methylation, specifically di-/tri-methylation. This regulation promotes gene silencing through heterochromatin formation. SETDB1 altered lymphocyte and cytokine expression, disrupts the IFN-I response, promotes TAM recruitment, induces ERV silencing, and facilitates tumor immune escape |
777166 |
