Cited by 92Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

Succinylation of H3K122 destabilizes nucleosomes and enhances transcription

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Zorro Shahidian, Lara, Haas, Mariska, Le Gras, Stephanie, Nitsch, Sandra, Mourão, André, Geerlof, Arie, Margueron, Raphael, Michaelis, Jens +2 more·2021·The EMBO Reports

Abstract

Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription. Using chromatin succinylated at H3K122 in in vitro transcription assays, we show that the presence of H3K122succ is sufficient to stimulate transcription. In line with this, we found in our ChIP assays H3K122succ enriched on promoters of active genes and H3K122succ enrichment scaling with gene expression levels. Furthermore, we show that the co-activators p300/CBP can succinylate H3K122 and identify sirtuin 5 (SIRT5) as a new desuccinylase. By applying single molecule FRET assays, we demonstrate a direct effect of H3K122succ on nucleosome stability, indicating an important role for histone succinylation in modulating chromatin dynamics. Together, these data provide the first insights into the mechanisms underlying transcriptional regulation by H3K122succ.

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  • In the vast majority of studies to date, histone succinylation is associated with the opening of chromatin and increased gene transcription.

    “In the vast majority of these studies to date, histone succinylation is associated with the opening of chromatin and increased gene transcription.”

    From Loss of succinyl-CoA synthetase in mouse forebrain results in hypersuccinylation with perturbed neuronal transcription and metabolism (2023) · cites this paper as [47]

    The Abstract reports that H3K122 succinylation stimulates transcription, and Results and Discussion (‘Succinylation of H3K122 decreases nucleosome stability’; page not provided) links it to increased DNA accessibility. The paper studies this specific modification; it does not establish that the vast majority of histone-succinylation studies find the same association. (LLM, conf=0.88)

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1 of the 67 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Hu A, Britton LM, Garcia BA (2014) Investigating the specificity of histone acetyltransferase activity for producing rare modifications on histones using mass spectrometry. In Proceedings of the 62nd Annual American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, Baltimore
  2. Schwarz MSK, Kallis E, Eustermann S, Guariento M, Moldt M, Hopfner K‐P, Michaelis J (2018) Single‐molecule nucleosome remodelling by INO80 and effects of histone tails. FEBS Lett 592: 318– 331 29331030

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Authors
Zorro Shahidian, L., Haas, M., Le Gras, S., Nitsch, S., Mourão, A., Geerlof, A., Margueron, R., Michaelis, J., Daujat, S., & Schneider, R.
Affiliations
  • Universität Ulm (DE)
  • Helmholtz Munich (DE)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Schneider, Robert
Venue
The EMBO Reports
Published
2021-01-29
Volume
22
Issue
3
Pages
e51009-e51009
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
OpenAlex
W3123068255
Cited by
92
References
67
Citations by year
2026: 18 · 2025: 28 · 2024: 18 · 2023: 10 · 2022: 13 · 2021: 5
FWCI
3.69
Type
journal article
Language
en
Open access
Locations
  • EMBO Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
  • HAL (submittedVersion, cc-by-nc-nd)
  • OPen Access Repositorium der Universität Ulm (OPARU) (Ulm University) (submittedVersion, cc-by-nc-nd)
  • Site cant be reached (submittedVersion, cc-by-nc-nd)
  • Universität Ulm, Kommunikations- und Informationszentrum (kiz)
Funders
  • Deutsche Forschungsgemeinschaft (286540087, CRC 1279, SFB 1064, SFB 1309)
  • Epitrio Consortium
  • Ampro Program (ZT0026)
  • Helmholtz Gesellschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
histone acylation, histone modifications, nucleosome stability, transcriptional regulation, SIRT5, chromatin dynamics, promoter, histone octamer
MeSH terms
Chromatin, Gene Expression Regulation, Histones, Nucleosomes, Protein Processing, Post-Translational

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