EC Number   |
General Information |
Reference |
|---|
   2.1.1.366 | physiological function |
SETDB1 is the bridge linking the DNA damage response to meiotic silencing in male mice. At the onset of silencing, X chromosome H3K9 trimethylation enrichment is downstream of DNA damage response factors. Without SETDB1, the X chromosome accrues DNA damage response proteins but not H3K9me3, so sex chromosome remodeling and silencing fail, causing germ cell apoptosis. Setdb1 deletion causes midpachytene apoptosis. SETDB1 is required for epigenetic remodeling of the XY pair, for condensation of the XY pair and for XY silencing at pachynema |
759112 |
| 2.1.1.366 | physiological function |
SETDB1 methylation regulates H3K9me3 in the OTX2 promoter region and inhibits the expression of OTX2. SETDB1 expression is downregulated in osteoporotic femoral tissues and is involved in osteogenic differentiation. Upregulation of SETDB1 promotes osteogenic differentiation by inhibiting OTX2 and activating the BMP-Smad and Wnt/beta-catenin pathways in osteoporosis |
777586 |
| 2.1.1.366 | physiological function |
SETDB1 regulates the development of cortical Htr3a-positive interneurons and mood behaviors |
776709 |
| 2.1.1.366 | physiological function |
SETDB1 regulates the PTEN/AKT/FOXO1 pathway to inhibit spermatogonial stem cell apoptosis. SETDB1 interacts and coordinates with AKT to regulate FOXO1 activity and expression of the downstream target genes Bim and Puma. Among the SETDB1-bound genes, the H3K9me3 levels on the promoter regions of Bim and Pten decrease in the SETDB1-knock down group. The H3K9me3 status on promoters of Bax and Puma remains unchanged |
758839 |
| 2.1.1.366 | physiological function |
SETDB1 strengthens non-small cell lung cancer cell migratory and invasive abilities by promoting invadopodia formation and extracellular matrix degradation. At the molecular level, SETDB1 suppresses the expression of FOXA2, a crucial tumor and metastasis suppressor via coordinated epigenetic mechanisms. SETDB1 not only catalyzes histone H3K9 methylation on FOXA2 genomic locus, but also recruits DNMT3A to regulate DNA methylation on CpG island. Setdb1 is essential for malignant progression and metastasis of murine lung adenocarcinoma |
778826 |
| 2.1.1.366 | physiological function |
the cytoplasmic fraction of the histone lysine methyltransferase Setdb1 is essential for survival of embryonic stem cells. Setdb1 interacts with many RNA-binding proteins and translation regulators such as Trim71. Setdb1 is required for Trim71 complex integrity cSetdb1 regulates the abundance of specific mRNAs, of which Trim71 and hnRNPc targets |
777831 |
| 2.1.1.366 | physiological function |
the enzyme is involved in heterochromatin formation and silencing of repeat elements |
778808 |
| 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 |
| 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 |
