Histone H3 phosphorylation near the nucleosome dyad alters chromatin structure
Open accessAbstract
Nucleosomes contain ∼146 bp of DNA wrapped around a histone protein octamer that controls DNA accessibility to transcription and repair complexes. Posttranslational modification (PTM) of histone proteins regulates nucleosome function. To date, only modest changes in nucleosome structure have been directly attributed to histone PTMs. Histone residue H3(T118) is located near the nucleosome dyad and can be phosphorylated. This PTM destabilizes nucleosomes and is implicated in the regulation of transcription and repair. Here, we report gel electrophoretic mobility, sucrose gradient sedimentation, thermal disassembly, micrococcal nuclease digestion and atomic force microscopy measurements of two DNA-histone complexes that are structurally distinct from nucleosomes. We find that H3(T118ph) facilitates the formation of a nucleosome duplex with two DNA molecules wrapped around two histone octamers, and an altosome complex that contains one DNA molecule wrapped around two histone octamers. The nucleosome duplex complex forms within short ∼150 bp DNA molecules, whereas altosomes require at least ∼250 bp of DNA and form repeatedly along 3000 bp DNA molecules. These results are the first report of a histone PTM significantly altering the nucleosome structure.
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The flexible N-terminal tails undergo reversible modifications that alter histone-DNA interactions and shift chromatin between active and repressive states.
“While the histone core contributes to nucleosome stability, the flexible N-terminal tails undergo reversible modifications that alter histone–DNA interactions and shift chromatin between active and repressive states (North et al., 2014).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as North et al., 2014
The Introduction (page unavailable) says most histone modifications occur on disordered N-terminal tails and can affect higher-order chromatin compaction. It attributes direct changes in histone–DNA interactions to modifications within the structured nucleosome core, not specifically to the tails. It does not describe tail modifications shifting chromatin between active and repressive states. (LLM, conf=0.87)
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“While the histone core contributes to nucleosome stability, the flexible N-terminal tails undergo reversible modifications that alter histone–DNA interactions and shift chromatin between active and repressive states (North et al., 2014).”
- Authors
- North, J. A., Šimon, M., Ferdinand, M. B., Shoffner, M. A., Picking, J. W., Howard, C. J., Mooney, A. M., van Noort, J., Poirier, M. G., & Ottesen, J. J.
- Affiliations
- Leiden University (NL)
- Corresponding author
- Ottesen, Jennifer J.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-02-21
- Volume
- 42
- Issue
- 8
- Pages
- 4922-4933
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4005658
- OpenAlex
- W2074165495
- Cited by
- 46
- References
- 53
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 7 · 2015: 3 · 2014: 5
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institute of General Medical Sciences (R01GM083055)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- histone H3 phosphorylation, nucleosome dyad, nucleosome structure, histone modifications, chromatin structure, histone-DNA complex
- MeSH terms
- Base Sequence, Chromatin, DNA, Histones, Nucleosomes, Phosphorylation, Threonine, Histone Chaperones
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