Evidence map›Paper›PMID 34012049›Full record

ArticleNature communications2021

Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin.

Young-Tae Lee, Alex Ayoub, Sang-Ho Park, Liang Sha, Jing Xu, Fengbiao Mao, Wei Zheng, Yang Zhang, Uhn-Soo Cho, Yali Dou

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  6. Probing the Cancer Mutational Landscape of KMT2 Regulatory Subunits.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. The FBXW7-KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Recent Progress of Protein Tertiary Structure Prediction.Molecules (Basel, Switzerland) · 2024
    Review
  17. Review
  18. Review
  19. KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1.Virchows Archiv : an international journal of pathology · 2023
    Article
  20. Review
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

10 authors at 2 institutions in 1 country.

Young-Tae LeeDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3522-9361
Alex AyoubDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Sang-Ho ParkDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Liang ShaDepartment of Medicine, Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA, USA.
Jing XuDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Fengbiao MaoDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Wei ZhengComputational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-2984-9003
Yang ZhangDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Uhn-Soo ChoDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
Yali DouDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA. yalidou@usc.edu.ORCID 0000-0002-4040-1429
University of Michigan · USUniversity of Southern California · US

Funding

Function of MLL in transcription regulationR01GM082856 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DOU, YALI · 2009 to 2023
$4.0M
Structural insights into the MLL core complexesR01CA250329 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHO, UHN-SOO, DOU, YALI · 2020 to 2024
$3.0M
NCI NIH HHS R01 CA250329NIGMS NIH HHS R01 GM082856
6 · The paper itself

Abstract

Recent cryo-EM structures show the highly dynamic nature of the MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation of such dynamics remain unclear. Here we show that DPY30 and the intrinsically disordered regions (IDRs) of ASH2L work together in restricting the rotational dynamics of the MLL1 complex on the NCP. We show that DPY30 binding to ASH2L leads to stabilization and integration of ASH2L IDRs into the MLL1 complex and establishes new ASH2L-NCP contacts. The significance of ASH2L-DPY30 interactions is demonstrated by requirement of both ASH2L IDRs and DPY30 for dramatic increase of processivity and activity of the MLL1 complex. This DPY30 and ASH2L-IDR dependent regulation is NCP-specific and applies to all members of the MLL/SET1 family of enzymes. We further show that DPY30 is causal for de novo establishment of H3K4me3 in ESCs. Our study provides a paradigm of how H3K4me3 is regulated on chromatin and how H3K4me3 heterogeneity can be modulated by ASH2L IDR interacting proteins.

Indexed as

AnimalsCell LineChromatinCryoelectron MicroscopyDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseHistonesHuman Embryonic Stem CellsHumansIntrinsically Disordered ProteinsIn Vitro TechniquesMagnetic Resonance SpectroscopyMiceModels, MolecularMouse Embryonic Stem CellsMyeloid-Lymphoid Leukemia ProteinASH2L protein, humanChromatinDNA-Binding ProteinsDPY30 protein, humanHistone-Lysine N-MethyltransferaseHistonesIntrinsically Disordered ProteinsKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinNuclear ProteinsNucleosomesSetd1A protein, humanTranscription Factors

Identifiers

PMID34012049
PMCPMC8134635
OpenAlexW3161542780

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.