Evidence map›Paper›PMID 39155390›Full record

ArticleClinical epigenetics2024

HDAC6 inhibition disrupts HDAC6-P300 interaction reshaping the cancer chromatin landscape.

Michela Gottardi Zamperla, Barbara Illi, Veronica Barbi, Chiara Cencioni, Daniele Santoni, Stella Gagliardi, Maria Garofalo, Gabriele Antonio Zingale, Irene Pandino, Diego Sbardella and 8 more

Abstract read
In one paragraph

Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. CRISPR-epigenetic crosstalk: From bidirectional regulation to therapeutic potential.Computational and structural biotechnology journal · 2025
    Review
  12. 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

18 authors.

Michela Gottardi Zamperla *Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy.
Barbara Illi *Institute of Molecular Biology and Pathology, National Research Council (CNR), c/o Sapienza University of Rome, 00185, Rome, Italy.
Veronica BarbiLaboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy.
Chiara CencioniInstitute for Systems Analysis and Computer Science, National Research Council (CNR)-IASI, 00185, Rome, Italy.
Daniele SantoniInstitute for Systems Analysis and Computer Science, National Research Council (CNR)-IASI, 00185, Rome, Italy.
Stella GagliardiMolecular Biology and Transcriptomics Unit, IRCCS Mondino Foundation, 27100, Pavia, Italy.
Maria GarofaloMolecular Biology and Transcriptomics Unit, IRCCS Mondino Foundation, 27100, Pavia, Italy.
Gabriele Antonio ZingaleIRCCS-Fondazione Bietti, Rome, Italy.
Irene PandinoIRCCS-Fondazione Bietti, Rome, Italy.
Diego SbardellaIRCCS-Fondazione Bietti, Rome, Italy.
Lina CipollaInstitute of Molecular Genetics, National Research Council (CNR), 27100, Pavia, Italy.
Simone SabbionedaInstitute of Molecular Genetics, National Research Council (CNR), 27100, Pavia, Italy.
Antonella FarsettiInstitute for Systems Analysis and Computer Science, National Research Council (CNR)-IASI, 00185, Rome, Italy.
Chiara RipamontiNew Drug Incubator Department, Italfarmaco Group, 20092, Cinisello Balsamo, Italy.
Gianluca FossatiNew Drug Incubator Department, Italfarmaco Group, 20092, Cinisello Balsamo, Italy.
Christian SteinkühlerNew Drug Incubator Department, Italfarmaco Group, 20092, Cinisello Balsamo, Italy.
Carlo GaetanoLaboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy. carlo.gaetano@icsmaugeri.it.
Sandra AtlanteInstitute for Systems Analysis and Computer Science, National Research Council (CNR)-IASI, 00185, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHistone deacetylases (HDACs) are crucial regulators of gene expression, DNA synthesis, and cellular processes, making them essential targets in cancer research. HDAC6, specifically, influences protein stability and chromatin dynamics. Despite HDAC6's potential therapeutic value, its exact role in gene regulation and chromatin remodeling needs further clarification. This study examines how HDAC6 inactivation influences lysine acetyltransferase P300 stabilization and subsequent effects on chromatin structure and function in cancer cells. METHODS AND

resultsWe employed the HDAC6 inhibitor ITF3756, siRNA, or CRISPR/Cas9 gene editing to inactivate HDAC6 in different epigenomic backgrounds. Constantly, this inactivation led to significant changes in chromatin accessibility, particularly increased acetylation of histone H3 lysines 9, 14, and 27 (ATAC-seq and H3K27Ac ChIP-seq analysis). Transcriptomics, proteomics, and gene ontology analysis revealed gene changes in cell proliferation, adhesion, migration, and apoptosis. Significantly, HDAC6 inactivation altered P300 ubiquitination, stabilizing P300 and leading to downregulating genes critical for cancer cell survival.

conclusionsOur study highlights the substantial impact of HDAC6 inactivation on the chromatin landscape of cancer cells and suggests a role for P300 in contributing to the anticancer effects. The stabilization of P300 with HDAC6 inhibition proposes a potential shift in therapeutic focus from HDAC6 itself to its interaction with P300. This finding opens new avenues for developing targeted cancer therapies, improving our understanding of epigenetic mechanisms in cancer cells.

Indexed as

ChromatinHistone Deacetylase 6Histone Deacetylase InhibitorsAcetylationCell Line, TumorCell ProliferationE1A-Associated p300 ProteinGene Expression Regulation, NeoplasticHistonesHumansNeoplasmsUbiquitinationChromatinE1A-Associated p300 ProteinEP300 protein, humanHDAC6 protein, humanHistone Deacetylase 6Histone Deacetylase InhibitorsHistonesApoptosisCancerCell cycleDeacetylase inhibitorsHATHDACHistone acetylationProliferationTumorigenesis

Identifiers

PMID39155390
PMCPMC11331611

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.