Evidence map›Paper›PMID 40518664›Full record

ArticleBiophysical journal2025

Structural and thermodynamic impact of oncogenic mutations on the nucleosome core particle.

Augustine C Onyema, Christopher DiForte, Rutika Patel, Sébastien F Poget, Sharon M Loverde

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biophysical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Mapping Allosteric Communication in the Nucleosome with Conditional Activity.Journal of chemical information and modeling · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Augustine C OnyemaPh.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York; Department of Chemistry, College of Staten Island, The City University of New York, 2800 Victory Boulevard, Staten Island, New York, New York.
Christopher DiFortePh.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York; Department of Chemistry, College of Staten Island, The City University of New York, 2800 Victory Boulevard, Staten Island, New York, New York.
Rutika PatelPh.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York; Department of Chemistry, College of Staten Island, The City University of New York, 2800 Victory Boulevard, Staten Island, New York, New York.
Sébastien F PogetPh.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York; Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York; Department of Chemistry, College of Staten Island, The City University of New York, 2800 Victory Boulevard, Staten Island, New York, New York.
Sharon M LoverdePh.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York; Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York; Ph.D. Program in Physics, The Graduate Center of the City University of New York, New York, New York; Department of Chemistry, College of Staten Island, The City University of New York, 2800 Victory Boulevard, Staten Island, New York, New York. Electronic address: sharon.loverde@csi.cuny.edu.

Funding

Breakthrough Molecular Dynamics Research via an Anton2 SupercomputerR01GM116961 · NIGMS · CARNEGIE-MELLON UNIVERSITY · PI BLOOD, PHILIP D. · 2016 to 2023
$3.0M
Computational Methods to Characterize Structure and Dynamics of the Nucleosome Core ParticleR15GM146228 · NIGMS · COLLEGE OF STATEN ISLAND · PI LOVERDE, SHARON MARIE · 2022 to 2023
$586k
Biophysical analysis of interactions between peptide toxins and human sodium channel voltage-sensor domainsR15GM141976 · NIGMS · COLLEGE OF STATEN ISLAND · PI POGET, SEBASTIEN F · 2022 to 2023
$534k
NIGMS NIH HHS R01 GM116961NIGMS NIH HHS R15 GM141976NIGMS NIH HHS R15 GM146228
6 · The paper itself

Abstract

The nucleosome core particle is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. Here, we investigate the molecular consequences of two mutations-H2BE76K and H4R92T-using 36 μs of all-atom molecular dynamics simulations and experimental biophysical assays. These mutations destabilize the H2B-H4 interface by disrupting critical salt bridges and hydrogen bonds, reducing binding free energy at this interface. Principal-component analysis reveals altered helix conformations and increased interhelical distances in mutant systems. Thermal stability assays and differential scanning calorimetry confirm that these mutations lower the dimer dissociation temperature and reduce enthalpy compared with the wild-type. Taken together, our results elucidate how these mutations compromise nucleosome stability and propose mechanisms through which they could modulate chromatin accessibility and gene dysregulation in cancer.

Indexed as

HistonesMutationNucleosomesOncogenesHumansMolecular Dynamics SimulationThermodynamicsHistonesNucleosomes

Identifiers

PMID40518664
PMCPMC12414687

What OpenQuestion holds

Textmetadata
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.