Evidence map›Paper›PMID 24465000›Full record

ArticleNucleic acids research2014

MLL fusion proteins link transcriptional coactivators to previously active CpG-rich promoters.

Hiroshi Okuda, Marie Kawaguchi, Akinori Kanai, Hirotaka Matsui, Takeshi Kawamura, Toshiya Inaba, Issay Kitabayashi, Akihiko Yokoyama

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

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.0field-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

39 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
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  4. Article
  5. HBO1, a MYSTerious KAT and its links to cancer.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024
    Review
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  8. Review
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  10. Article
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  14. Review
  15. Article
  16. Article
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  18. Review
  19. Roles of SETD2 in Leukemia-Transcription, DNA-Damage, and Beyond.International journal of molecular sciences · 2019
    Review
  20. Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2018
    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

8 authors at 3 institutions in 1 country.

Hiroshi OkudaLaboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan, Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan and Department of Molecular Biology and Medicine, Laboratory for System Biology and Medicine (LSBM), Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
Marie Kawaguchi
Akinori Kanai
Hirotaka Matsui
Takeshi Kawamura
Toshiya Inaba
Issay Kitabayashi
Akihiko Yokoyama
Kyoto University · JPHiroshima University · JPThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mixed-lineage leukemia (MLL) maintains the expression of cellular memory genes during development, while leukemic MLL fusion proteins aberrantly maintain expression of hematopoietic stem cell program genes such as HOXA9 to cause leukemia. However, the molecular mechanism of gene activation is unclear. Here we show that only two functional modules are necessary and sufficient for target recognition: those that bind to non-methylated CpGs and di-/tri-methylated histone H3 lysine 36 (H3K36me2/3). An artificial protein composed of the two targeting modules and an interaction domain for AF4-family coactivators can functionally substitute for MLL fusion proteins. Because H3K36me2/3 markers are indicative of active transcription, MLL fusion proteins target previously active CpG-rich genes and activate transcription by recruiting coactivators thereto. Our results indicate that such chromatin context-dependent gene activation is the fundamental mechanism by which MLL fusion proteins maintain the expression of the cellular memory/hematopoietic stem cell program genes.

Indexed as

CpG IslandsPromoter Regions, GeneticTranscriptional ActivationAnimalsCell Line, TumorCell Transformation, NeoplasticHistonesHumansLeukemia, ExperimentalMiceMice, Inbred C57BLMyeloid-Lymphoid Leukemia ProteinNucleosomesOncogene Proteins, FusionProtein Structure, TertiaryTrans-ActivatorsHistonesMyeloid-Lymphoid Leukemia ProteinNucleosomesOncogene Proteins, FusionTrans-Activators

Identifiers

PMID24465000
PMCPMC3985622
OpenAlexW2123810432

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.