Evidence map›Paper›PMID 41634341›Full record

ArticleNature cell biology2026

DOT1L provides transcriptional memory through PRC1.1 antagonism.

Daniel Neville, Daniel T Ferguson, Emily B Heikamp, Zhihao Lai, Graham W Magor, Charlene Lam, Olivia G Dobbs, Vita Levina, Kathy Knezevic, James J The and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

21 authors.

Daniel Neville *Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Daniel T Ferguson *Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Emily B HeikampDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Zhihao LaiMater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Graham W MagorAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Charlene LamAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Olivia G DobbsAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Vita LevinaMater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Kathy KnezevicPeter MacCallum Cancer Centre and the University of Melbourne, Parkville, Victoria, Australia.
James J TheAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Shania AlexAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Stephen C SuitsAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Bradon RumlerAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Michael UckelmannMater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Laure TalarmainPeter MacCallum Cancer Centre and the University of Melbourne, Parkville, Victoria, Australia.
Enid Y N LamPeter MacCallum Cancer Centre and the University of Melbourne, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0001-5843-7836
Andrew C PerkinsAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0003-3644-7093
Scott A ArmstrongDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9099-4728
Charles C BellMater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.ORCID http://orcid.org/0000-0003-2194-8311
Chen DavidovichDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. chen.davidovich@monash.edu.ORCID http://orcid.org/0000-0002-1085-6094
Omer GilanAustralian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia. omer.gilan@monash.edu.ORCID http://orcid.org/0000-0003-4156-2619

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Epigenetic regulators define a dynamic chromatin landscape in NUP98-rearranged leukemiaK08CA279891 · NCI · DANA-FARBER CANCER INST · PI EMILY HEIKAMP · 2024 to 2026
$646k
Department of Health | National Health and Medical Research Council (NHMRC) 1146192Department of Health | National Health and Medical Research Council (NHMRC) APP1162921Department of Health | National Health and Medical Research Council (NHMRC) APP1184637Department of Health | National Health and Medical Research Council (NHMRC) APP2011767Department of Health | National Health and Medical Research Council (NHMRC) APP2020900NCI NIH HHS K08 CA279891NCI NIH HHS P01 CA066996NCI NIH HHS P30 CA006516U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA066996U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30 CA06516Victorian Cancer Agency (VCA) MCRF19040
6 · The paper itself

Abstract

DOT1L and Menin are essential cofactors for the oncogenic activity of MLL fusion proteins (MLL-FPs) in leukaemia. However, the mechanisms underpinning the therapeutic effects of their inhibitors remain unclear. Here we identify a critical role for the non-canonical Polycomb repressive complex 1.1 (PRC1.1) in mediating the cellular responses to DOT1L and Menin inhibitors. Menin inhibition induces PRC1.1-dependent deposition of H2AK119ub to silence a subset of MLL-FP targets, whereas DOT1L inhibition results in a genome-wide increase in H2AK119ub. We show that enhanced PRC1.1 activity arises specifically from the progressive loss of DOT1L-mediated H3K79 methylation, independent of MLL-FP displacement or transcriptional repression. This regulatory crosstalk is conserved across cell types and is driven by direct biochemical antagonism between H3K79 methylation and PRC1 activity. Together, our findings establish DOT1L as a component of transcriptional memory co-opted in leukaemia and suggest it serves as the missing link balancing the opposing forces of the MLL-Polycomb axis.

Indexed as

Histone-Lysine N-MethyltransferaseLeukemiaMethyltransferasesPolycomb Repressive Complex 1Proto-Oncogene ProteinsTranscription, GeneticAnimalsCell Line, TumorHistonesHumansMethylationMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionDOT1L protein, humanHistone-Lysine N-MethyltransferaseHistonesMEN1 protein, humanMethyltransferasesMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPolycomb Repressive Complex 1Proto-Oncogene Proteins

Identifiers

PMID41634341
PMCPMC12904788

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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.