Evidence map›Paper›PMID 30392929›Full record

ArticleMolecular cell2018

Critical Role of the UBL Domain in Stimulating the E3 Ubiquitin Ligase Activity of UHRF1 toward Chromatin.

Benjamin M Foster, Paul Stolz, Christopher B Mulholland, Alex Montoya, Holger Kramer, Sebastian Bultmann, Till Bartke

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

57 citing papers in PubMed, 93 citations in OpenAlex.

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  12. Germline variants inProceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Benjamin M FosterInstitute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; MRC London Institute of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
Paul StolzDepartment of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilians University (LMU Munich), 82152 Planegg-Martinsried, Germany.
Christopher B MulhollandDepartment of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilians University (LMU Munich), 82152 Planegg-Martinsried, Germany.
Alex MontoyaMRC London Institute of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK.
Holger KramerMRC London Institute of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK.
Sebastian BultmannDepartment of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilians University (LMU Munich), 82152 Planegg-Martinsried, Germany.
Till BartkeInstitute of Functional Epigenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; MRC London Institute of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address: till.bartke@helmholtz-muenchen.de.
Center for Integrated Protein Science Munich · DEHelmholtz Zentrum München · DEMRC London Institute of Medical Sciences · GB

Funding

European Research Council 309952Medical Research Council MC_UP_1102/2
6 · The paper itself

Abstract

The RING E3 ubiquitin ligase UHRF1 controls DNA methylation through its ability to target the maintenance DNA methyltransferase DNMT1 to newly replicated chromatin. DNMT1 recruitment relies on ubiquitylation of histone H3 by UHRF1; however, how UHRF1 deposits ubiquitin onto the histone is unknown. Here, we demonstrate that the ubiquitin-like domain (UBL) of UHRF1 is essential for RING-mediated H3 ubiquitylation. Using chemical crosslinking and mass spectrometry, biochemical assays, and recombinant chromatin substrates, we show that the UBL participates in structural rearrangements of UHRF1 upon binding to chromatin and the E2 ubiquitin conjugating enzyme UbcH5a/UBE2D1. Similar to ubiquitin, the UBL exerts its effects through a hydrophobic patch that contacts a regulatory surface on the "backside" of the E2 to stabilize the E2-E3-chromatin complex. Our analysis of the enzymatic mechanism of UHRF1 uncovers an unexpected function of the UBL domain and defines a new role for this domain in DNMT1-dependent inheritance of DNA methylation.

Indexed as

AnimalsCCAAT-Enhancer-Binding ProteinsChromatinDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationHEK293 CellsHistonesHumansMaleMiceMouse Embryonic Stem CellsNuclear ProteinsProtein BindingUbiquitinUbiquitinationCCAAT-Enhancer-Binding ProteinsChromatinDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesHistonesNuclear ProteinsUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUHRF1 protein, humanUhrf1 protein, mousechromatinDNA methylationhistone modificationubiquitin-like foldubiquitylationUHRF1

Identifiers

PMID30392929
PMCPMC6242706
OpenAlexW2899151145

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.