Evidence map›Paper›PMID 41125851›Full record

ArticleThe EMBO journal2025

Functional landscape of ubiquitin linkages couples K29-linked ubiquitylation to epigenome integrity.

Javier Arroyo-Gomez, Matthew J Murray, Claire Guérillon, Juanjuan Wang, Ekaterina Isaakova, Nazaret Reverón-Gómez, Mikaela Koutrouli, Aldwin Suryo Rahmanto, Katrine Mitrofanov, Andreas Ingham and 12 more

Abstract read
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

22 authors.

Javier Arroyo-GomezNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0009-0003-7751-1853
Matthew J Murray *Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-0379-7161
Claire Guérillon *Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-1982-6596
Juanjuan Wang *Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Ekaterina IsaakovaInstitute of Molecular Biology, 55218, Mainz, Germany.
Nazaret Reverón-GómezNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-7347-781X
Mikaela KoutrouliNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Aldwin Suryo RahmantoInstitute of Molecular Biology, 55218, Mainz, Germany.
Katrine MitrofanovNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0009-0009-2181-5552
Andreas InghamNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Sofie SchovsboNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Katrine WeischenfeldtNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Fabian CosciaNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-2244-5081
Dimitris TypasNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Moritz Völker-AlbertEpiQMAx GmbH, Planegg, Germany.
Victor SolisEpiQMAx GmbH, Planegg, Germany.
Lars Juhl JensenNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Anja GrothNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.
Andreas MundNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-7843-5341
Petra BeliInstitute of Molecular Biology, 55218, Mainz, Germany.
Robert F ShearerNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark. robert.shearer@cpr.ku.dk.ORCID http://orcid.org/0000-0003-3012-8788
Niels MailandNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200, Copenhagen, Denmark. niels.mailand@cpr.ku.dk.ORCID http://orcid.org/0000-0002-6623-709X

Funding

Danish Cancer Society R316-A19079Danmarks Frie Forskningsfond (DFF) 9040-00038BEC | Horizon 2020 Framework Programme (H2020) 846795EC | Horizon 2020 Framework Programme (H2020) 860517 (UBIMOTIF)Lundbeck Foundation (Lundbeckfonden) R223-2016-281Lundbeck Foundation (Lundbeckfonden) R402-2022-1321Novo Nordisk Fonden (NNF) NNF14CC0001Novo Nordisk Fonden (NNF) NNF24SA0098829
6 · The paper itself

Abstract

Linkage-specific ubiquitin chains govern the outcome of numerous critical ubiquitin-dependent signaling processes, but their targets and functional impacts remain incompletely understood due to a paucity of tools for their specific detection and manipulation. Here, we applied a cell-based ubiquitin replacement strategy enabling targeted conditional abrogation of each of the seven lysine-based ubiquitin linkages in human cells to profile system-wide impacts of disabling formation of individual chain types. This revealed proteins and processes regulated by each of these poly-ubiquitin topologies and indispensable roles of K48-, K63- and K27-linkages in cell proliferation. We show that K29-linked ubiquitylation is strongly associated with chromosome biology, and that the H3K9me3 methyltransferase SUV39H1 is a prominent cellular target of this modification. K29-linked ubiquitylation catalyzed by TRIP12 and reversed by TRABID constitutes the essential degradation signal for SUV39H1 and is primed and extended by Cullin-RING ubiquitin ligase activity. Preventing K29-linkage-dependent SUV39H1 turnover deregulates H3K9me3 homeostasis but not other histone modifications. Collectively, these data resources illuminate cellular functions of linkage-specific ubiquitin chains and establish a key role of K29-linked ubiquitylation in epigenome integrity.

Indexed as

Epigenesis, GeneticEpigenomeLysineMethyltransferasesRepressor ProteinsUbiquitinUbiquitinationHEK293 CellsHistonesHumansUbiquitin-Protein LigasesHistonesLysineMethyltransferasesRepressor ProteinsSUV39H1 protein, humanUbiquitinUbiquitin-Protein LigasesEpigenome maintenanceHeterochromatinLinkage-specific ubiquitylationUbiquitinUbiquitin-dependent proteolysis

Identifiers

PMID41125851
PMCPMC12669653

What OpenQuestion holds

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Registered trials

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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.