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bioRxiv · 10.1101/422360

The Oligomerization Landscape of Histones

Zhao, H.·Winogradoff, D.·Dalal, Y.·Papoian, G.
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Abstract

In eukaryotes, DNA is packaged through nucleosomes. Each nucleosome is typically centered around an octameric histone protein core: one central tetramer plus two separate dimers. Studying the assembly mechanisms of histones is essential for understanding the dynamics of entire nucleosomes and higher-order DNA packaging. Here we investigate the canonical histone assembly and that of the centromere-specific histone variant CENP-A using molecular dynamics simulations. We quantitatively characterize their thermodynamical and dynamical features, showing that the canonical H3 tetramer exhibits large instability around the central interface manifested via a swiveling motion of two halves, supporting the recently observed DNA handedness flipping of the tetrasome. In contrast, the variant CENP-A encodes a distinctive stability to its tetramer with a rigid but twisted interface compared to the crystal structure, implying the diverse structural possibilities of the histone variant. Interestingly, the observed tetramer dynamics alter significantly and appear to reach a new dynamics balance when H2A/H2B dimers are present. In all, these data reveal key mechanistic insights and structural details for the assembly of canonical and variant CENP-A histone tetramers and octamers, providing theoretical quantifications and physical interpretations for longstanding and recent experimental observations.

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Zhao, H., Winogradoff, D., Dalal, Y., Papoian, G.. 2018-09-20. The Oligomerization Landscape of Histones. https://doi.org/10.1101/422360

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