Evidence map›Paper›PMID 30981630›Full record

ArticleMolecular cell2019

Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination.

Marco Igor Valencia-Sánchez, Pablo De Ioannes, Miao Wang, Nikita Vasilyev, Ruoyu Chen, Evgeny Nudler, Jean-Paul Armache, Karim-Jean Armache

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

100 citing papers in PubMed, 162 citations in OpenAlex.

  1. Precision Chemistry for Protein Lysine Modification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  2. Article
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  19. Discovery and structural studies of histone demethylases.Frontiers in epigenetics and epigenomics · 2025
    Review
  20. Article

40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Marco Igor Valencia-SánchezSkirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Pablo De IoannesSkirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Miao WangSkirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Nikita VasilyevDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Ruoyu ChenSkirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Evgeny NudlerDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Jean-Paul ArmacheDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Karim-Jean ArmacheSkirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: karim-jean.armache@nyulangone.org.
New York University · USHoward Hughes Medical Institute · USUniversity of California, San Francisco · US

Funding

Molecular Structure Determination by Mass Spectrometry and Computational ModelingR01GM127267 · NIGMS · UNIVERSITY OF MISSISSIPPI · PI Joshua S Sharp · 2018 to 2026
$3.8M
Structural and functional analysis of gene silencingR01GM115882 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARMACHE, KARIM JEAN · 2015 to 2023
$3.4M
NIGMS NIH HHS R01 GM115882NIGMS NIH HHS R01 GM127267
6 · The paper itself

Abstract

The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the detailed mechanism is not understood. We report cryo-EM structures of human Dot1L bound to (1) H2BK120Ub and (2) unmodified nucleosome substrates at 3.5 Å and 4.9 Å, respectively. Comparison of both structures, complemented with biochemical experiments, provides critical insights into the mechanism of Dot1L stimulation by H2BK120Ub. Both structures show Dot1L binding to the same extended surface of the histone octamer. In yeast, this surface is used by silencing proteins involved in heterochromatin formation, explaining the mechanism of their competition with Dot1. These results provide a strong foundation for understanding conserved crosstalk between histone modifications found at actively transcribed genes and offer a general model of how ubiquitin might regulate the activity of chromatin enzymes.

Indexed as

Protein ConformationBinding SitesCryoelectron MicroscopyGenome, HumanGenomic InstabilityHeterochromatinHistone-Lysine N-MethyltransferaseHistonesHumansLeukemiaLysineNuclear ProteinsNucleosomesProtein BindingSaccharomyces cerevisiae ProteinsTranscription, GeneticDOT1L protein, humanDot1 protein, S cerevisiaeHeterochromatinHistone-Lysine N-MethyltransferaseHistonesLysineNuclear ProteinsNucleosomesSaccharomyces cerevisiae Proteinschromatincryo-EMDot1H3K79histone cross-talkhistone modificationsmethylationnucleosomestructureubiquitin

Identifiers

PMID30981630
PMCPMC7009778
OpenAlexW2939146474

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.