Cited by 93Genomics and Chromatin DynamicsNuclear Structure and FunctionEpigenetics and DNA Methylation

Histone Core Phosphorylation Regulates DNA Accessibility

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Brehove, Matthew, Wang, Tao, North, Justin, Luo, Yi, Dreher, Sarah J., Shimko, John C., Ottesen, Jennifer J., Luger, Karolin +1 more·2015·Journal of Biological Chemistry

Abstract

Nucleosome unwrapping dynamics provide transient access to the complexes involved in DNA transcription, repair, and replication, whereas regulation of nucleosome unwrapping modulates occupancy of these complexes. Histone H3 is phosphorylated at tyrosine 41 (H3Y41ph) and threonine 45 (H3T45ph). H3Y41ph is implicated in regulating transcription, whereas H3T45ph is involved in DNA replication and apoptosis. These modifications are located in the DNA-histone interface near where the DNA exits the nucleosome, and are thus poised to disrupt DNA-histone interactions. However, the impact of histone phosphorylation on nucleosome unwrapping and accessibility is unknown. We find that the phosphorylation mimics H3Y41E and H3T45E, and the chemically correct modification, H3Y41ph, significantly increase nucleosome unwrapping. This enhances DNA accessibility to protein binding by 3-fold. H3K56 acetylation (H3K56ac) is also located in the same DNA-histone interface and increases DNA unwrapping. H3K56ac is implicated in transcription regulation, suggesting that H3Y41ph and H3K56ac could function together. We find that the combination of H3Y41ph with H3K56ac increases DNA accessibility by over an order of magnitude. These results suggest that phosphorylation within the nucleosome DNA entry-exit region increases access to DNA binding complexes and that the combination of phosphorylation with acetylation has the potential to significantly influence DNA accessibility to transcription regulatory complexes.

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Crossref · 10.1074/jbc.m115.661363

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Authors
Brehove, M., Wang, T., North, J., Luo, Y., Dreher, S. J., Shimko, J. C., Ottesen, J. J., Luger, K., & Poirier, M. G.
Affiliations
  • The Ohio State University (US)
  • Colorado State University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Poirier, Michael G.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2015-09
Volume
290
Issue
37
Pages
22612-22621
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1567904427
Cited by
93
References
65
Citations by year
2026: 5 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 11 · 2021: 12 · 2020: 7 · 2019: 14 · 2018: 12 · 2017: 5 · 2016: 12 · 2015: 3
FWCI
4.63
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (5p01gm088409-05)
  • National Institute of General Medical Sciences (GM 088409, R01GM083055, GM083055, P01- GM088409, R01GM105404, R01GM096192)
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 › Epigenetics and DNA Methylation
Keywords
histone H3 phosphorylation, H3K56 acetylation, nucleosome unwrapping, DNA accessibility, histone modifications, transcriptional regulation, DNA replication, apoptosis
MeSH terms
Acetylation, DNA, Histones, Humans, Nucleosomes, Phosphorylation, Transcription, Genetic

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