- EMDB-22694: Active state Dot1 bound to the H4K16ac nucleosome, Ubiquitin focu... -
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Basic information
Entry
Database: EMDB / ID: EMD-22694
Title
Active state Dot1 bound to the H4K16ac nucleosome, Ubiquitin focused map
Map data
Active state Dot1L bound to the H4K16 acetylated nucleosome, Ub focused
Sample
Complex: Active state Dot1 bound to the H4K16 acetylated nucleosome
Complex: Histones
Protein or peptide: Histone H3.2
Protein or peptide: Histone H4
Protein or peptide: Histone H2A type 1
Protein or peptide: Histone H2B 1.1
Complex: Histone-lysine N-methyltransferase, H3 lysine-79 specific
Protein or peptide: Histone-lysine N-methyltransferase, H3 lysine-79 specific
Complex: Polyubiquitin-B
Protein or peptide: Polyubiquitin-B
Complex: DNA (146-MER)
DNA: DNA (146-MER)
DNA: DNA (146-MER)
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 / recombinational repair / mitotic intra-S DNA damage checkpoint signaling ...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 / recombinational repair / mitotic intra-S DNA damage checkpoint signaling / subtelomeric heterochromatin formation / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / mitotic G1 DNA damage checkpoint signaling / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / TNFR1-induced NF-kappa-B signaling pathway / DNA damage checkpoint signaling / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / Regulation of NF-kappa B signaling / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / NOTCH3 Activation and Transmission of Signal to the Nucleus / Negative regulators of DDX58/IFIH1 signaling / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / 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 / nucleotide-excision repair / Fanconi Anemia Pathway / Negative regulation of FGFR3 signaling / Hh mutants are degraded by ERAD / Recognition of DNA damage by PCNA-containing replication complex / Peroxisomal protein import / Degradation of AXIN / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Regulation of TNFR1 signaling Similarity search - Function
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
5R01GM115882-03
United States
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
Deposition
Sep 21, 2020
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Header (metadata) release
Feb 10, 2021
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Map release
Feb 10, 2021
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Update
Feb 10, 2021
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Current status
Feb 10, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 297 K / Instrument: FEI VITROBOT MARK IV
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Electron microscopy
Microscope
FEI TITAN KRIOS
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: 1809 / Average exposure time: 10.0 sec. / Average electron dose: 74.5 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
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