Evidence map›Paper›PMID 41044756›Full record

ArticleEpigenetics & chromatin2025

Disruption of histone acetylation homeostasis reveals multilayered chromatin regulation for transcriptional resiliency.

Vrinda Venu, Eric M Small, Cullen Roth, Samantha H Adikari, Anna Hendrika Cornelia Vlot, Kyle A Sullivan, Chanaka Roshan Abeyratne, Daniel Jacobson, Shawn R Starkenburg, Karissa Y Sanbonmatsu and 1 more

Abstract read
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Article in Epigenetics & chromatin, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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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

11 authors.

Vrinda VenuGenomics and Bioanalytics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Eric M SmallGenomics and Bioanalytics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Cullen RothGenomics and Bioanalytics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Samantha H AdikariBiochemistry and Biotechnology Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Anna Hendrika Cornelia VlotComputational and Predictive Biology Group, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Kyle A SullivanComputational and Predictive Biology Group, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Chanaka Roshan AbeyratneComputational and Predictive Biology Group, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Daniel JacobsonComputational and Predictive Biology Group, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
Shawn R StarkenburgGenomics and Bioanalytics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Karissa Y SanbonmatsuTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Christina R SteadmanGenomics and Bioanalytics Group, Los Alamos National Laboratory, Los Alamos, NM, USA. crsteadman@lanl.gov.

Funding

Biological and Environmental Research 89233218CNA000001Laboratory Directed Research and Development 20210082DRLaboratory Directed Research and Development 20210134EROffice of Science DE-AC05-00OR22725
6 · The paper itself

Abstract

backgroundEpigenetic modifications, nucleosome occupancy, and three-dimensional chromatin architecture collectively create a multi-layered, highly interactive regulatory system for controlling genomic functionality. Dysregulation of epigenetic processes leads to a plethora of abnormalities including disease states. Therapies focused on epigenetic modulation can alter gene expression to correct dysfunction, though the perpetuation of these states and the relationships among chromatin regulatory layers is not well understood.

resultsHere, we investigated global and local chromatin structural and functional responses after acute histone deacetylase inhibitor treatment (suberoylanilide hydroxamic acid) in lung cancer cells across time. Treatment substantially increased global histone acetylation resulting in a pervasive but not distinctive signature. The spread of acetylation did not significantly impact global chromatin accessibility, and nucleosome remodeling largely occurred at finer scales in functionally relevant genomic regions. Indeed, both H3K4 trimethylation, a mark of active transcription, and gene expression changes were altered in a controlled locus-specific manner, suggesting aberrant acetylation indirectly leads to balanced and bidirectional gene expression profiles from tighter regulation of other chromatin features. HDACi treatment induced (13%) genomic rearrangement in chromatin compartmentalization and moderate weakening of topologically associating domains.

conclusionsContinuous wavelet analysis of these features demonstrates that scale-dependent, locus-specific factors influence the relationship between chromatin architecture and functional output, suggesting that regulation of transcription and nucleosome remodeling is not entirely (nor linearly) dependent upon large scale compartment exchange. Structural and functional responses are most pronounced early after treatment with partial persistence of differential local chromatin features and expression later in time; this highlights the plasticity of chromatin regulation, which may have implications for the efficacy of epigenetic treatments. These results demonstrate the effectiveness of multi-layered regulation of transcription: in resilient systems, disruption of one chromatin feature does not distort the regulation of other features in supporting a transcriptional program that allows for survival.

Indexed as

ChromatinHistonesTranscription, GeneticAcetylationCell Line, TumorChromatin Assembly and DisassemblyEpigenesis, GeneticHistone Deacetylase InhibitorsHomeostasisHumansNucleosomesVorinostatChromatinHistone Deacetylase InhibitorsHistonesNucleosomesVorinostatChromatin accessibilityChromatin architectureEpigenetic resiliencyEpigenetic therapeuticsFunctional epigenomicsHDAC inhibitionHistone acetylationMultiscale chromatin organizationNucleosome remodelingTranscriptional dynamics

Identifiers

PMID41044756
PMCPMC12492967

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LicenceCC BY-NC-ND
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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.