Evidence map›Paper›PMID 37626123›Full record

ArticleNature communications2023

MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia.

Nicholas T Crump, Alastair L Smith, Laura Godfrey, Ana M Dopico-Fernandez, Nicholas Denny, Joe R Harman, Joseph C Hamley, Nicole E Jackson, Catherine Chahrour, Simone Riva and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Is Enhancer Function Driven by Protein-Protein Interactions? From Bacteria to Leukemia.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  8. Review
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  10. Review
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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

22 authors at 6 institutions in 3 countries.

Nicholas T Crump *MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK. n.crump@imperial.ac.uk.ORCID http://orcid.org/0000-0001-9610-6763
Alastair L Smith *MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0001-6330-1407
Laura GodfreyMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Ana M Dopico-FernandezMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0009-0007-7314-3319
Nicholas DennyMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Joe R HarmanMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0003-3668-1859
Joseph C HamleyMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Nicole E JacksonMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0009-0005-2096-6878
Catherine ChahrourMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0002-8326-5260
Simone RivaMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Siobhan RiceMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Jaehoon KimDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.ORCID http://orcid.org/0000-0003-4035-0438
Venkatesha BasrurDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Damian FerminDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Kojo Elenitoba-JohnsonDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Robert G RoederLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-3865-8572
C David AllisLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-7589-713X
Irene RobertsMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Anindita RoyMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.ORCID http://orcid.org/0000-0001-8607-5748
Huimin GengDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
James O J DaviesMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Thomas A MilneMRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK. thomas.milne@imm.ox.ac.uk.ORCID http://orcid.org/0000-0002-0413-4271
University of Oxford · GBRockefeller University · USUniversity of Michigan · USKorea Advanced Institute of Science and Technology · KRUniversity of California, San Francisco · USUniversity of Pennsylvania · US

Funding

Medical Research Council MC_UU_00016/6Medical Research Council MC_UU_00029/4Medical Research Council MC_UU_00029/6Medical Research Council MC_UU_00029/7Medical Research Council MR/R006237/1Medical Research Council MR/R008108/1
6 · The paper itself

Abstract

Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.

Indexed as

LeukemiaNuclear ProteinsBromodomain Containing ProteinsCell Cycle ProteinsHumansMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPromoter Regions, GeneticRegulatory Sequences, Nucleic AcidTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsMLL-AF4 fusion protein, humanMyeloid-Lymphoid Leukemia ProteinNuclear ProteinsOncogene Proteins, FusionPAF1 protein, humanTranscription Factors

Identifiers

PMID37626123
PMCPMC10457349
OpenAlexW4386157047

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.