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Yorodumi- EMDB-22695: Active state Dot1 bound to the unacetylated H4 nucleosome, Ubiqui... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22695 | |||||||||
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Title | Active state Dot1 bound to the unacetylated H4 nucleosome, Ubiquitin focused map | |||||||||
Map data | Active state Dot1L bound to the H4K16 unacetylated nucleosome | |||||||||
Sample |
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Function / homology | Function and homology information negative regulation of heterochromatin formation / PKMTs methylate histone lysines / meiotic recombination checkpoint signaling / histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / global genome nucleotide-excision repair / postreplication repair / mitotic intra-S DNA damage checkpoint signaling / recombinational repair ...negative regulation of heterochromatin formation / PKMTs methylate histone lysines / meiotic recombination checkpoint signaling / histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / global genome nucleotide-excision repair / postreplication repair / mitotic intra-S DNA damage checkpoint signaling / recombinational repair / subtelomeric heterochromatin formation / Maturation of protein E / Maturation of protein E / mitotic G1 DNA damage checkpoint signaling / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / FLT3 signaling by CBL mutants / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Glycogen synthesis / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Endosomal Sorting Complex Required For Transport (ESCRT) / TICAM1,TRAF6-dependent induction of TAK1 complex / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of FZD by ubiquitination / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / p75NTR recruits signalling complexes / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / InlA-mediated entry of Listeria monocytogenes into host cells / Regulation of pyruvate metabolism / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Pexophagy / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of PTEN localization / Regulation of BACH1 activity / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / TICAM1, RIP1-mediated IKK complex recruitment / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / PINK1-PRKN Mediated Mitophagy / IKK complex recruitment mediated by RIP1 / Regulation of activated PAK-2p34 by proteasome mediated degradation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / InlB-mediated entry of Listeria monocytogenes into host cell / DNA damage checkpoint signaling / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / TNFR1-induced NF-kappa-B signaling pathway / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Regulation of NF-kappa B signaling / SCF-beta-TrCP mediated degradation of Emi1 / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / activated TAK1 mediates p38 MAPK activation / TNFR2 non-canonical NF-kB pathway / Vpu mediated degradation of CD4 / Negative regulators of DDX58/IFIH1 signaling / nucleotide-excision repair / NOTCH3 Activation and Transmission of Signal to the Nucleus / Assembly of the pre-replicative complex / Degradation of DVL / Deactivation of the beta-catenin transactivating complex / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Fanconi Anemia Pathway / Negative regulation of FGFR3 signaling / Hh mutants are degraded by ERAD / Degradation of AXIN / Peroxisomal protein import / Activation of NF-kappaB in B cells / Regulation of TNFR1 signaling Similarity search - Function | |||||||||
Biological species | Saccharomyces cerevisiae (brewer's yeast) / Xenopus laevis (African clawed frog) / Homo sap (brewer's yeast) / Synthetic (others) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Valencia-Sanchez MI / De Ioannes PE / Miao W / Truong DM / Lee R / Armache J-P / Boeke JD / Armache K-J | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Science / Year: 2021 Title: Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation. Authors: Marco Igor Valencia-Sánchez / Pablo De Ioannes / Miao Wang / David M Truong / Rachel Lee / Jean-Paul Armache / Jef D Boeke / Karim-Jean Armache / Abstract: Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide ...Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo. These data reveal mechanisms that control H3K79 methylation and demonstrate how H4K16ac, H3K79me, and H2BUb function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22695.map.gz | 95.5 MB | EMDB map data format | |
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Header (meta data) | emd-22695-v30.xml emd-22695.xml | 31.5 KB 31.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_22695_fsc.xml | 10.1 KB | Display | FSC data file |
Images | emd_22695.png | 95.9 KB | ||
Others | emd_22695_additional_1.map.gz emd_22695_half_map_1.map.gz emd_22695_half_map_2.map.gz | 95.4 MB 59.7 MB 59.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22695 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22695 | HTTPS FTP |
-Validation report
Summary document | emd_22695_validation.pdf.gz | 538.8 KB | Display | EMDB validaton report |
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Full document | emd_22695_full_validation.pdf.gz | 538.4 KB | Display | |
Data in XML | emd_22695_validation.xml.gz | 16.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22695 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22695 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_22695.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Active state Dot1L bound to the H4K16 unacetylated nucleosome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.035 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Unsharpened Active state Dot1L bound to the H4K16...
File | emd_22695_additional_1.map | ||||||||||||
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Annotation | Unsharpened Active state Dot1L bound to the H4K16 unacetylated nucleosome | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map Active state Dot1L bound to the...
File | emd_22695_half_map_1.map | ||||||||||||
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Annotation | Half map Active state Dot1L bound to the H4K16 unacetylated nucleosome | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map Active state Dot1L bound to the...
File | emd_22695_half_map_2.map | ||||||||||||
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Annotation | Half map Active state Dot1L bound to the H4K16 unacetylated nucleosome | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Active state Dot1 bound to the unacetylated H4 nucleosome
+Supramolecule #1: Active state Dot1 bound to the unacetylated H4 nucleosome
+Supramolecule #2: Histones
+Supramolecule #3: Histone-lysine N-methyltransferase, H3 lysine-79 specific
+Supramolecule #4: Polyubiquitin-B
+Supramolecule #5: DNA (146-MER)
+Macromolecule #1: Histone H3.2
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1
+Macromolecule #4: Histone H2B 1.1
+Macromolecule #5: Histone-lysine N-methyltransferase, H3 lysine-79 specific
+Macromolecule #6: Polyubiquitin-B
+Macromolecule #7: DNA (146-MER)
+Macromolecule #8: DNA (146-MER)
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.45 mg/mL | |||||||||||||||
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Buffer | pH: 7 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE Details: 3.0 uL of the samples at 0.45 mg/mL concentration were applied Quantifoil gold grids (400 mesh, 1.2 um hole size). The grids were previously glow-discharged 30s. After sample application, ...Details: 3.0 uL of the samples at 0.45 mg/mL concentration were applied Quantifoil gold grids (400 mesh, 1.2 um hole size). The grids were previously glow-discharged 30s. After sample application, the grids were blotted for 3s using Vitrobot Mark IV (FEI Company)at 4o C and 100 percent of humidity. The grids were subsequently plunge-frozen in liquid ethane cooled to liquid nitrogen temperatures. | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 297 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Sampling interval: 5.0 µm / Number grids imaged: 1 / Number real images: 4031 / Average exposure time: 8.0 sec. / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |