EC Number   |
General Information |
Reference  |
|---|
   2.1.1.366 | physiological function |
Setdb1 in macrophages potently suppresses Toll-like receptor TLR4-mediated expression of proinflammatory cytokines including interleukin-6 through its methyltransferase activity. Setdb1-deficiency decreases the basal H3K9 methylation levels and augments TLR4-mediated NF-kappaB recruitment on the proximal promoter region of interleukin-6, thereby accelerating interleukin-6 promoter activity. Macrophage-specific Setdb1-knockout mice exhibit higher serum interleukin-6 concentrations in response to lipopolysaccharide challenge and are more susceptible to endotoxin shock than wild-type mice |
755432 |
| 2.1.1.366 | physiological function |
ATFa-associated factor mAM stimulates ESET enzymatic activity by increasing the Vmax and decreasing the Km. mAM facilitates the ESET-dependent conversion of dimethyl H3-K9 to the trimethyl state both in vitro and in vivo. mAM enhances ESET-mediated transcriptional repression in a SAM-dependent manner, and this repression correlates with histone H3-K9 trimethylation at the promoter |
757646 |
| 2.1.1.366 | physiological function |
ESET interacts with transcription factor EST |
757872 |
| 2.1.1.366 | physiological function |
bivalend combinantion, dually marked histones H3K9me3/H3K14ac modification in the liver, is significantly decreased in old hepatocytes. A correlation between H3K9me3/H3K14ac bulk bivalent genomic regions and dually marked single nucleosomes is suggested. Histone H3K9 deacetylase Hdac3, as well as H3K9 methyltransferase Setdb1, found in complex Kap1, occupy both bulk and single nucleosome bivalent regions in both young and old livers, correlating to presence of H3K9me3. Expression of genes associated with bivalent regions in young liver, including those regulating cholesterol secretion and triglyceride synthesis, is upregulated in old liver once the bivalency is lost |
758617 |
| 2.1.1.366 | physiological function |
deletion of Setdb1 in Meckel's cartilage tissue leads to its enlargement. Chondrocytes from the Meckel's cartilage of Setdb1 conditional KO mice show increased size. At embryonic days 16.5 and 18.5, part of the perichondrium is disrupted and mineralization is observed in the Meckel's cartilage. Inhibition of Setdb1 causes increased proliferation in chondrocytes in the Meckel's cartilage as well as in siRNA-treated ATDC5 cells. Decreased expression of chondrogenic genes, such as Sox9, Mmp13, Collagen II, and Aggrecan, is observed as a result of Setdb1 inhibition in ATDC5 cells. SMAD-dependent BMP signaling is significantly increased by the loss of Setdb1 in both the Meckel's cartilage of Setdb1 conditional KO mice and siRNA-treated ATDC5 cells |
758727 |
| 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 |
embryonic stem cells exhibit high expression of the ubiquitin-conjugating enzyme UBE2K. Loss of UBE2K upregulates the trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation |
759079 |
| 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 is an epigenetic regulator of primordial germ cell fate determination. SETDB1-deficient embryos exhibit drastic reduction of nascent primordial germ cells. Dppa2, Otx2 and Utf1 are derepressed whereas mesoderm development-related genes, including BMP4 signaling-related genes, are downregulated by SETDB1 knockdown during primordial germ cell-like cell induction. Binding of SETDB1 is observed at the flanking regions of Dppa2, Otx2 and Utf1 in cell aggregates containing primordial germ cell-like cell induction, and trimethylation of lysine 9 of histone H3 is reduced by SETDB1 knockdown at those regions |
759113 |
| 2.1.1.366 | physiological function |
microRNA, miR-152-3p is involved in the regulation of SETDB1 protein levels and plays a positive regulatory role for SETDB1 expression. Inhibition of miR-152-3p results in a robust reduction in SETDB1 protein levels, though SETDB1 mRNA levels are unaffected. This is accompanied by a blockade of the biochemical pathway proceeding from H3K9me2 to H3K9me3. H3K9me2 accumulates in cells treated with an anti-miR that targets miR-152-3p. The action of a miR-152-3p mimic increases flux of the reaction leading to H3K9me3 |
759155 |
