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J Biol Chem. 2015 Sep 11;290(37):22612-21. doi: 10.1074/jbc.M115.661363. Epub 2015 Jul 13.

Histone core phosphorylation regulates DNA accessibility.

Author information

1
From the Department of Physics.
2
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523.
3
Department of Microbiology.
4
Biophysics Graduate Program.
5
Ohio State Biochemistry Program, and.
6
Ohio State Biochemistry Program, and Department of Chemistry and Biochemistry, The Ohio State University, Columbus Ohio 43210 and.
7
Biophysics Graduate Program, Ohio State Biochemistry Program, and Department of Chemistry and Biochemistry, The Ohio State University, Columbus Ohio 43210 and.
8
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523 the Howard Hughes Medical Institute and.
9
From the Department of Physics, Biophysics Graduate Program, Ohio State Biochemistry Program, and Department of Chemistry and Biochemistry, The Ohio State University, Columbus Ohio 43210 and mpoirier@mps.ohio-state.edu.

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.

KEYWORDS:

DNA accessibility; DNA-protein interaction; fluorescence resonance energy transfer (FRET); histone modification; histone post-translational modifications; nucleosome; small-angle X-ray scattering (SAXS)

PMID:
26175159
PMCID:
PMC4566235
DOI:
10.1074/jbc.M115.661363
[Indexed for MEDLINE]
Free PMC Article

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