SETDB1 activity is globally directed by H3K14 acetylation via its Triple Tudor Domain
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PROVIDER: PRJNA1088534 | ENA |
REPOSITORIES: ENA
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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: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:H3K14ac is linked to methylation of H3K9 by the Tudor domains of SETDB1
| PRJEB15097 | ENA
Project description:KAT8 is a lysine acetyltransferase and is involved in multiple important biological processes including cancer. The well-known function of KAT8 is catalyzing acetylation on histone H4, which regulates gene expression and chromatin decompaction. Besides catalytic HAT domain, the function of Tudor-knot domain of KAT8 remains largely unclear. Here, we report a novel function of Tudor-knot domain in facilitates histone acetyltransferase activity on H4K16ac. One hot-spot cancer mutation on Tudor-knot domain of KAT8 inhibits its interaction with nucleosome and reduces H4K16ac level both in vitro and in cells without altering the chromatin occupancy. Interestingly, this Tudor-knot mutation does not influence acetylation activity of KAT8 on p53, a non-histone substrate, suggests the important function of KAT8 Tudor-knot domain in the substrate specific catalytic regulation.
2023-12-24 | GSE245008 | GEO
Project description:KAT8 is a lysine acetyltransferase and is involved in multiple important biological processes including cancer. The well-known function of KAT8 is catalyzing acetylation on histone H4, which regulates gene expression and chromatin decompaction. Besides catalytic HAT domain, the function of Tudor-knot domain of KAT8 remains largely unclear. Here, we report a novel function of Tudor-knot domain in facilitates histone acetyltransferase activity on H4K16ac. One hot-spot cancer mutation on Tudor-knot domain of KAT8 inhibits its interaction with nucleosome and reduces H4K16ac level both in vitro and in cells without altering the chromatin occupancy. Interestingly, this Tudor-knot mutation does not influence acetylation activity of KAT8 on p53, a non-histone substrate, suggests the important function of KAT8 Tudor-knot domain in the substrate specific catalytic regulation.
2023-12-24 | GSE245007 | 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: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.
2024-01-26 | PXD037104 | Pride
Project description:Setdb1 is an epigenetic factors catalyzing modification of H3K9me3. Expression of its gene is localized to embryonic neural cells during vertebrate embryogenesis, suggesting its role in regulating neural stemness. The project is to identify the interaction partners of Setdb1, by which Setdb1 regulates neural stemness in neural stem cells.
2022-08-12 | PXD030453 | Pride
Project description:ChIP-seq experiment for histone H3 and H3K4me3 from wild-type Saccharomyces cerevisiae (WT) and strains in which H3K14 has been substituted for alanine (K14A) or H3P16 has been substituted with valine (P16V).
2014-07-22 | E-MTAB-2717 | biostudies-arrayexpress
Project description:we report DPF2 and H3K14 modifications in K562 cells
2020-12-01 | GSE112967 | GEO