Evidence map›Paper›PMID 40683254›Full record

ArticleMolecular cell2025

Structural mechanism of H3K27 demethylation and crosstalk with heterochromatin markers.

Chien-Chu Lin, Yani Zhao, Caroline A Foley, Aspen T Hawkins, Lindsey I James, Stephen V Frye, Robert K McGinty

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. 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

7 authors.

Chien-Chu LinCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yani ZhaoCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Caroline A FoleyCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Aspen T HawkinsDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lindsey I JamesCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Stephen V FryeCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Robert K McGintyCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: rmcginty@email.unc.edu.

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Molecular Mechanisms of Chromatin RecognitionR35GM133498 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Robert McGinty · 2019 to 2026
$3.3M
PROBING ALLOSTERY IN METHYL-LYSINE READER DOMAINSR35GM139514 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRYE, STEPHEN VERNON · 2021 to 2025
$2.1M
NCI NIH HHS P30 CA016086NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R35 GM133498NIGMS NIH HHS R35 GM139514
6 · The paper itself

Abstract

Histone H3 lysine 27 trimethylation (H3K27me3) is a repressive histone modification that is a hallmark of facultative heterochromatin. H3K27me3 is installed by the polycomb repressive complex 2 (PRC2) and removed by KDM6 family Jumonji C (JmjC) domain demethylases. Structural studies have elucidated how PRC2 functions on nucleosomes and its regulation by local histone modification signatures. However, the molecular mechanisms governing H3K27 demethylation to reactivate silenced chromatin remain poorly understood. Here, we report the cryoelectron microscopy (cryo-EM) structure of mouse KDM6B bound to the nucleosome. Our structure shows how KDM6B engages wrapped nucleosomal DNA together with both extranucleosomal DNA linkers to position its catalytic JmjC domain for H3K27 demethylation. KDM6B induces an overlapped linker DNA conformation consistent with function in a compact chromatin environment. We further show that linker histones and H2AK119ub1, both enriched in heterochromatin, antagonize KDM6B function, suggesting that linker histone eviction and H2A deubiquitylation precede H3K27 demethylation during heterochromatin activation.

Indexed as

HeterochromatinHistonesJumonji Domain-Containing Histone DemethylasesAnimalsCryoelectron MicroscopyDemethylationDNAHumansMethylationMiceModels, MolecularNucleosomesPolycomb Repressive Complex 2Protein BindingDNAHeterochromatinHistonesJumonji Domain-Containing Histone DemethylasesKdm6b protein, mouseNucleosomesPolycomb Repressive Complex 2chromatincryo-EMepigeneticsH3K27me3heterochromatinhistoneKDM6Blysine demethylasenucleosomepost-translation modification

Identifiers

PMID40683254
PMCPMC12333602

What OpenQuestion holds

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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.