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- Table of Contents
Facts about Histone-lysine N-methyltransferase SETDB1.
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.
Human | |
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Gene Name: | SETDB1 |
Uniprot: | Q15047 |
Entrez: | 9869 |
Belongs to: |
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class V-like SAM-binding methyltransferase superfamily |
ERG-associated protein with SET domain; ESETEC 2.1.1.43; H3-K9-HMTase 4; Histone H3-K9 methyltransferase 4; histone-lysine N-methyltransferase SETDB1; histone-lysine N-methyltransferase, H3lysine-9 specific 4; KG1T; KIAA0067H3-K9-HMTase4; KMT1EERG-associated protein with a SET domain, ESET; Lysine N-methyltransferase 1E; SET domain bifurcated 1; SET domain, bifurcated 1
Mass (kDA):
143.157 kDA
Human | |
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Location: | 1q21.3 |
Sequence: | 1; NC_000001.11 (150926263..150964737) |
Widely expressed. High expression in testis.
Nucleus. Cytoplasm. Chromosome. Associated with non-pericentromeric regions of chromatin. Excluded from nucleoli and islands of condensed chromatin.
SETDB1 refers to a gene involved with DNA methylation, and repression. SETDB1 antibodies are made from a single or multiple monoclonal antibodies that react with this gene in a variety species of mammals and other species. Boster Bio produces its SETDB1 antibodies using rabbit and mouse samples. SETDB1 trimethylates Lys-9 on histone H3 in concert with DNA methylation. SETDB1 methylated represses transcription, and couples DNA methylation with histone trimethylation.
The SETDB1 SETDB1 marker is a commonly used marker in biological assays. There are many antibodies available that react with SETDB1 in a variety animal samples. Boster Bio has created SETDB1 antibodies to detect a mutated SETDB1 gene. SETDB1 trimethylates Lys-9 in histone H3, which coordinates with DNA methylation. This complex represses transcription by coupling DNA methylation and histone trimethylation.
SETDB1 is a gene regulatory protein that recruits H3K9 methyltransferase to target putative promoters and enhancers of a particular gene. SETDB1 represses a target genome by increasing local H3K9me3 bind. BosterBio: Best Uses of The SETDB1 Symbol
H3K9me3 is not yet fully understood in relation to DNA methylation. Although this gene is involved DNA methylation it may also play a role in genome stability and radiation resistance. It has been shown to be involved in maintaining DNA methylation. H3K9 trimethylation in ES cells is therefore important. Its exact role is not known.
Aaron Straight and his colleagues from different universities led the study that led to the discovery about the role of H3K9me3 within gene regulation. The team included Whitney Johnson and William Yewdell as joint first authors. The researchers discovered that RNAs from the vicinity of centromeres persist within the same cells where they were produced and co-localize with H3K9me3 heterochromatin marks. These scientists discovered that Boster Bio's H3K9me3 is linked to cells that are about to divide.
This is why H3K9me3 has the ability to interact with ubiquitin. H3K9me3 ubiquitin binding sites are different from Kme3 receptors. The H3-peptide is located between N and C of the bDNMT1RFTSdomain and is surrounded and protected by a PHD Finger domain. The binding of H3K9me3 results is a slight shift within the indole-ring, which eventually leads to an increase in the buried surface.
The SETDB1 IgG by Boston Bio is a monoclonal antibody against mice that has been tested for use with IF, IHC, WB applications. It reacts with Human, Mouse, and Rat. You can purchase the Boster Bio Anti-SETDB1 antibody from a variety sources. It has been shown to be effective against endogenous p63 levels of SETDB1.
TGF-b-induced EMT resulted in a reduction in SETDB1 expression. This suggests that SETDB1 inhibits EMT. However cells can easily inhibit SETDB1 and complete EMT. Moreover, SETDB1 knockdown induced ferroptosis. H3K9me3 expression was also reduced. Understanding the epigenetic mechanisms that lead to pulmonary fibrillis could be helped by SETDB1 involvement.
SETDB1 plays a number of critical roles in development, including regulating gene Expression. The gene has a genome-wide binding site in mouse ES cells. These binding locations overlap with Polycomb proteins, and the inter-protein JARID2.
SETDB1 acts as a nuclear localization regulator complex and contains a FNIIIdomain, which is critical for the suppression retroelement transcription. Exogenous expressions of 3xFLAG–ATF7IP were found to rescue SETDB1-induced abnormally localization in Atf7ip KO mESCs. We present quantitative analyses with DAPI staining, B and D, for SETDB1 as well as 3xFLAG -ATF7IP signal signals. The bar graph depicts the mean of three independent experiments. In the jittered points, the average intensities are from each experiment. We analysed more than 100 cells in three experiments.
Flag-SETDB1 was analyzed using LC/MS/MS. It was found that ubiquitination occurred at lysine-867(K867). This ubiquitination spot is essential for transcriptional suppression of SETDB1. The mutant containing FNIII domain did no such effect. The SETDB1-FL mESCs co-expressed with HA-Ub were similarly de-repressed in a single experiment.
The 6-aa SETDB1-K867 peptide was found less effective at binding to ubiquitin than longer proteins. However, the interactions of SETDB1 with ubiquitin moiety indicate that SETDB1 binding is a factor in SETDB1 ubiquitination. This binding may play an important role in positioning E2Ub thioester which is critical for Ub transfer. Interestingly, SETDB1 also harbors an unusually large insertion, which may contribute to the enzymatic activity of the protein.
Boster Bio SETDB1 SETDB1 MgM Kit allows you to measure SETDB1 IgG levels in your sample by separating soluble globulins. Boster Bio SETDB1 Kit contains antibodies to human SETDB1 as well as mouse SETDB1. This antibody was used in immunoprecipitation assays. This kit is compatible to various cell lines and can be used in the lab.
The SETDB1 Quantitative Kit IgG was validated on breast cancer cell line lines. In MCF-7 and HCC-1954 cells, si-SETDB1 cells were transfected with Flag-tagged DNp63a. To determine if the exogenous proteins bind endogenous SetDB1, immunoprecipitated the proteins. These data revealed a specific interaction of SETDB1 with DNp63a. This was confirmed by Western blot analysis using MCF-7 human breast cancer cells and MCF-10A normal human epidermal keratinocytes.
Boster Bio SETDB1 IgM test was used to confirm that a SETDB1 IgM antibody was specific for a given target. This assay also measures IgG levels in serum. SETDB1 is an important protein that is implicated in many types of cancer. In addition to breast cancer, SETDB1 has also been implicated in lung tumors and melanoma. It has been shown that this antibody is overexpressed in a chromosome segment that is recurrently amplified.
The SETDB1 marker is a H3K9-related protein that is monoubiquitinated in K867 by UBE2EE2 enzymes. UBE2E-conjugated UBEDB1 exhibits distinct characteristics from its monoubiquitination partner. SETDB1K867Ub1 can be catalyzed via UBE2E1 using promiscuous selectivity with lysine.
SETDB1 is monoubiquitinated by UBE2E enzymes at lysine 867, without the use of E3 ligases. SETDB1's SETdomain contains a large insertion that could confer its correct conformation. K867 monoubiquitination, which is essential for SETDB1's enzymatic activities, is crucial for mediated H3K9 methylation in murine embryonic cells stem cells.
The SETDB1 protein is found in the 5’ LTR of two different ERVs. The expression of SETDB1 has been affected by pharmacological treatments to the mouse mutagenesis models. SETDB1 can also be monoubiquitinated at K867. The SETDB1 genome is a novel biomarker of human ERVs. It is a promising marker for monitoring therapy and assessing disease progression.
Flag-SETDB1-(D528-584) was co-expressed in 293T cells along with UBE2E1 and 13 DUBs. Flag-SETDB1 was co-expressed alongside HA-Ub -wt and Ub-K0. Flag-SETDB1wt was coexpressed with Ub-K0 or HA-Ub–wt to identify deubiquitinated proteins.
PMID: 11959841 by Schultz D.C., et al. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins.
PMID: 12869583 by Ayyanathan K., et al. Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation.