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Structural dynamics of nucleosome mediated by acetylations at H3K56 and H3K115,122

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Abstract

Post translational modifications have a profound role in the regulation of several biological processes such as transcription, replication, and DNA repair. Acetylation and phosphorylation form a major class of post translational modifications involved in nucleosomal regulation by modifying its structure. The effect of post translational modifications on nucleosome structure could be better explored when the molecular trajectories explaining the time dependent structural evolution over a period of time is examined at the atomic level. The present study attempts to highlight the importance of acetylation, especially at entry–exit (Lys56) and dyad (Lys115 and Lys122) regions in regulating the nucleosome accessibility and mobility using all atom simulations. It is evident from this study that acetylation at Lys56, Lys115, and Lys122 introduces local changes in the electrostatic nature of the lateral surface and thereby weakens the histone–DNA interactions. In addition, simulations also reveal significant changes in the dynamics of superhelical DNA. The acetylation at Lys56 promotes a high amplitude out-of-planar movement of entry–exit termini. Whereas, acetylation at Lys115 and Lys122 increases the flexibility of the superhelical DNA to facilitate the rolling of the superhelical DNA around the octameric histone. In essence, the present study highlights the role of acetylation at Lys56, Lys115, and Lys122 in transcriptional regulation by promoting high amplitude dynamics of superhelical DNA for a possible unwrapping as well as mobility of nucleosome.

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Abbreviations

Aly:

Acetyllysine

PTM:

Post-translational modification

SHL:

Super helix location

MD:

Molecular dynamics

PCA:

Principle component analysis

RESP:

Restrained electrostatic potential

RDF:

Radial distribution function

SASA:

Solvent accessible surface area

FEL:

Free energy landscape

NUCwt :

Wildtype nucleosome

NUC56 :

Acetylated nucleosome H3K56

NUC115,122 :

Acetylated nucleosome H3K115,122

RMSD:

Root mean square deviation

Rg:

Radius of gyration

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Acknowledgements

One of the authors, Ramaswamy Amutha, acknowledges the Science and Engineering Research Board, India, for the financial support in the form of Fast Track Scheme for Young Scientists (SR/FT/LS-33/2010). The authors declare no conflict of interest.

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Authors and Affiliations

  1. Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry, 605014, India

    Muthukumaran Rajagopalan, Sangeetha Balasubramanian & Amutha Ramaswamy

  2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada

    Ilya Ioshikhes

  3. Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada

    Ilya Ioshikhes

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  1. Muthukumaran Rajagopalan
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  2. Sangeetha Balasubramanian
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  3. Ilya Ioshikhes
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  4. Amutha Ramaswamy
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Correspondence to Amutha Ramaswamy.

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Rajagopalan, M., Balasubramanian, S., Ioshikhes, I. et al. Structural dynamics of nucleosome mediated by acetylations at H3K56 and H3K115,122. Eur Biophys J 46, 471–484 (2017). https://doi.org/10.1007/s00249-016-1191-5

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