H3K14ac is linked to methylation of H3K9 by the Tudor domains of SETDB1
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB15097 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1562560.fastq.gz | Fastqsanger.gz | |||
| ERR1562561.fastq.gz | Fastqsanger.gz | |||
| ERR1562556.fastq.gz | Fastqsanger.gz | |||
| ERR1562557.fastq.gz | Fastqsanger.gz | |||
| ERR1562558.fastq.gz | Fastqsanger.gz |
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Project description:Mononucleosomes were isolated from murine ES cells and precipitated with the recombinant SETDB1 Triple Tudor Domain (3TD), recombinant SETDB1 Triple Tudor domain Y268A mutant, anti-H3K9me2 (Abcam, ab1220), or anti-H3K9me1 (Abcam, ab8896, Lot GR185298-1) antibodies.
2018-07-30 | E-MTAB-4982 | biostudies-arrayexpress
Project description:SETDB1 is a major H3K9 methyltransferase. It contains a unique Triple Tudor Domain (3TD) which specifically bind the dual modification of H3K14ac in the presence of H3K9me1/2/3. In this study, we explored the role of the 3TD H3K14ac interaction in the H3K9 methylation activity by SETDB1. We generated the 3TD binding reduced F332A mutant and demonstrate in biochemical methylation assays on recombinant nucleosomes containing H3K14ac analogs, that H3K14 acetylation is crucial for the 3TD mediated recruitment of SETDB1. We also see this effect in the cells where SETDB1 binding and activity was globally correlated with H3K14ac, and knock-out (KO) of the H3K14 acetyltransferase HBO1 caused a drastic reduction in the H3K9me3 levels at SETDB1 dependent sites. Further analyses revealed that 3TD was not required for SETDB1 recruitment for regions targeted by KAP1, but at specific target regions, SETDB1 KO could not be efficiently reconstituted by a 3TD mutant of SETDB1 as shown by the finding that H3K9 methylation of L1M repeat elements is highly dependent on an intact 3TD. In summary, our data demonstrate an important role of the 3TD interaction with H3 tails containing K14ac and K9 methylation in the recruitment of SETDB1 to chromatin which is particularly relevant at L1M repeats.
2024-11-15 | GSE261744 | GEO
Project description:The establishment of heterochromatin is a crucial process in the early embryonic development. Recent research suggests that SetDB1 is necessary for heterochromatin establishment in the early embryonic development of Drosophila. Additionally, SetDB1 has been found to bind to H3K14ac in mammalian cells. However, the role of the H3K14ac in heterochromatin establishment during embryogenesis remains unknown. Here we discovered that the active modification H3K14ac serves as an intergenerational marker from oocytes to early embryos, and it is recognized by Eggless/SetDB1 through its Tudor domains. Furthermore, we have introduced a point-mutation in the endogenous Eggless/SetDB1 locus, resulting in the loss of H3K14ac-binding. Both H3K14ac attenuation and SetDB1 mutant embryos exhibit abnormal heterochromatin formation and genomic instability. We reveal a novel model of heterochromatin establishment via H3K14ac-mediated recruitment of SetDB1.
2024-08-06 | GSE242239 | GEO
Project description:SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2. Mutations in the K14ac/K9me binding sites change the sub-nuclear localization of 3TD. ChIP-seq analyses show that SETDB1 is enriched at H3K9me3 regions and K9me3/K14ac is enriched at SETDB1 binding sites overlapping with LINE elements, suggesting that recruitment of the SETDB1 complex to K14ac/K9me regions has a role in silencing of active genomic regions.
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Project description:Post-translational modifications of histone tails play a crucial role in gene regulation. Here, we performed chromatin profiling by quantitative targeted mass spectrometry to assess all possible modifications of the core histones. We discovered a novel bivalent combination, a dually-marked H3K9me3/H3K14ac modification in the liver, that is significantly decreased in old hepatocytes. Subsequent genome-wide location analysis (ChIP-Seq) identified 1032 and 668 bivalent regions in young and old livers, respectively, with 280 in common. Histone H3K9 deacetylase Hdac3, as well as H3K9 methyltransferase Setdb1, found in complex Kap1, occupied 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. Hence, H3K9me3/H3K14ac dually-marked regions define a poised inactive state that is resolved with loss of one or both of the chromatin marks, which subsequently leads to change in gene expression.
2019-12-02 | GSE130712 | GEO
Project description:Histone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and overlaps well with lamina-associated domains and the B compartment defined by Hi-C. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear. We investigated genome-wide H3K9me2 distribution, transcriptome, and 3D genome organization in mouse embryonic stem cells following the inhibition or depletion of five H3K9 methyltransferases (MTases): G9a, GLP, SETDB1, SUV39H1, and SUV39H2. H3K9me2 was regulated by all five MTases; however, H3K9me2 and transcription in the A and B compartments were regulated by different MTases. H3K9me2 in A compartments was primarily regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments was regulated by all five MTases. Furthermore, decreased H3K9me2 correlated with changes to the more active compartmental state that accompanied transcriptional activation.
2021-08-05 | PXD024756 | Pride
Project description:Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins (PHD) and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element (TE)-derived double-stranded RNAs (dsRNAs), thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.
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Project description:Setdb1 regulates Cohesin at H3K9me3-independent topological domains
| PRJNA507948 | ENA
Project description:Three distinct enzymes are known to be capable of methylating lysine 9 residue of the histone H3 in Drosophila melanogaster: Su(var)3-9, SetDB1, and G9a. Here, we explored functional specialization of the two of them: SetDB1 and Su(var)3-9. Using DamID approach, we generated the binding profile for SetDB1 in salivary gland chromosomes, and matched it to the previously published profile of Su(var)3-9. Unlike Su(var)3-9, SetDB1 is an euchromatic protein that is absent from repeated DNA compartment, and is largely restricted to TSSes and 5'UTRs of moderately active ubiquitously expressed genes. Significant SetDB1 association is also observed at or near insulator protein CP190 binding sites. Extensive, yet not exact colocalization SetDB1 with Su(var)3-9 occurs only along the chromosome 4. Importantly, SetDB1 and H3K9me2/3-enriched sites tend to display poor overlap. At the same time, SetDB1 has clear connection with the distribution of H3K27me3 mark. SetDB1 binds outside the domains possessing this modification, and about half of the borders of H3K27me3 domains are decorated by SetDB1 binding sites together with actively transcribed genes. Given that SetDB1 displays low correlation with H3K9 methylation and binds to the TSSes of active genes, that are usually nucleosome-poor, we speculate that in somatic cells, SetDB1 may contribute to the methylation of a broader set of chromosomal proteins than just H3K9. In addition, via association with insulator proteins and transcription machinery, SetDB1 can be expected to play a role in the establishment of chromatin functional domains.
2020-08-04 | GSE155579 | GEO
Project description:Three distinct enzymes are known to be capable of methylating lysine 9 residue of the histone H3 in Drosophila melanogaster: Su(var)3-9, SetDB1, and G9a. Here, we explored functional specialization of the two of them: SetDB1 and Su(var)3-9. Using DamID approach, we generated the binding profile for SetDB1 in salivary gland chromosomes, and matched it to the previously published profile of Su(var)3-9. Unlike Su(var)3-9, SetDB1 is an euchromatic protein that is absent from repeated DNA compartment, and is largely restricted to TSSes and 5'UTRs of moderately active ubiquitously expressed genes. Significant SetDB1 association is also observed at or near insulator protein CP190 binding sites. Extensive, yet not exact colocalization SetDB1 with Su(var)3-9 occurs only along the chromosome 4. Importantly, SetDB1 and H3K9me2/3-enriched sites tend to display poor overlap. At the same time, SetDB1 has clear connection with the distribution of H3K27me3 mark. SetDB1 binds outside the domains possessing this modification, and about half of the borders of H3K27me3 domains are decorated by SetDB1 binding sites together with actively transcribed genes. Given that SetDB1 displays low correlation with H3K9 methylation and binds to the TSSes of active genes, that are usually nucleosome-poor, we speculate that in somatic cells, SetDB1 may contribute to the methylation of a broader set of chromosomal proteins than just H3K9. In addition, via association with insulator proteins and transcription machinery, SetDB1 can be expected to play a role in the establishment of chromatin functional domains.
2020-08-04 | GSE155580 | GEO