Evidence map›Paper›PMID 39704107›Full record

ArticleNucleic acids research2025

Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription.

David M English, Samuel N Lee, Khadija A Sabat, India M Baker, Trong Khoa Pham, Mark O Collins, Shaun M Cowley

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Engineering robustSynthetic and systems biotechnology · 2025
    Article
  8. Article
  9. Review
  10. Synergistic Antioxidant Effects of C3G-EnrichedInternational journal of molecular sciences · 2025
    Article
  11. 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.

David M EnglishDepartment of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Leicester, LE1 7RH, United Kingdom.
Samuel N LeeDepartment of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Leicester, LE1 7RH, United Kingdom.
Khadija A SabatDepartment of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Leicester, LE1 7RH, United Kingdom.
India M BakerCambridge Stem Cell Institute & Department of Haematology, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, Cambridge, CB2 0AW, United Kingdom.
Trong Khoa PhamSchool of Biosciences, University of Sheffield, Sheffield, S10 2TN, United Kingdom.
Mark O CollinsSchool of Biosciences, University of Sheffield, Sheffield, S10 2TN, United Kingdom.ORCID 0000-0002-7656-4975
Shaun M CowleyDepartment of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Leicester, LE1 7RH, United Kingdom.ORCID 0000-0002-2510-1305

Funding

BBSRC BB/P021689/1Medical Research Council MR/W00190X/1Midlands Integrative Biosciences Training Partnership (MIBTP)MRC MR/W00190X/1MRC IMPACT
6 · The paper itself

Abstract

Histone Deacetylase 1 (HDAC1) removes acetyl groups from lysine residues on core histones, a critical step in regulating chromatin accessibility. Despite histone deacetylation being an apparently repressive activity, suppression of HDACs causes both up- and downregulation of gene expression. Here we exploited the degradation tag (dTAG) system to rapidly degrade HDAC1 in mouse embryonic stem cells (ESCs) lacking its paralog, HDAC2. The dTAG system allowed specific degradation and removal of HDAC1 in <1 h (100x faster than genetic knockouts). This rapid degradation caused increased histone acetylation in as little as 2 h, with H2BK5 and H2BK11 being the most sensitive. The majority of differentially expressed genes following 2 h of HDAC1 degradation were upregulated (275 genes up versus 15 down) with increased proportions of downregulated genes observed at 6 h (1153 up versus 443 down) and 24 h (1146 up versus 967 down), respectively. Upregulated genes showed increased H2BK5ac and H3K27ac around their transcriptional start site (TSS). In contrast, decreased acetylation and chromatin accessibility of super-enhancers was linked to the most strongly downregulated genes. These findings suggest a paradoxical role for HDAC1 in the maintenance of histone acetylation levels at critical enhancer regions required for the pluripotency-associated gene network.

Indexed as

Gene Expression RegulationHistone Deacetylase 1Transcription, GeneticAcetylationAnimalsChromatinHistone Deacetylase 2HistonesMiceMouse Embryonic Stem CellsProteolysisChromatinHdac1 protein, mouseHdac2 protein, mouseHistone Deacetylase 1Histone Deacetylase 2Histones

Identifiers

PMID39704107
PMCPMC11879047

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.