Modulation of the DNA accessibility in the nucleosome -- insights from basic physics.

The nucleosome, a complex of 147 base-pairs of DNA with eight histone proteins, must protect its DNA, but, at the same time, allow on-demand access to it when needed by the cell. The exact mechanism of the control remain unclear.

A simplified electrostatic model of the nucleosome reveals that at physiological conditions the complex is extremely stable, but at the same time is close to the phase boundary separating it from the “unwrapped" states where the DNA is accessible. A small drop in the charge (e.g. through acetylation of a lysine) of the globular histone core can significantly lower nucleosome stability, and thus increase DNA accessibility. The finding suggests that charge-altering post-translational modifications in the histone core might be utilized by the cell to modulate accessibility to its DNA at the nucleosome level.

A follow-up, detailed multi-state atomistic model explores virtually all possible charge-altering post-translational modifications (PTMs) in the globular histone core. The model reveals a rich and nuanced picture: the effect of PTMs varies greatly depending on location, including counter-intuitive trends such as decrease of DNA accessibility for some lysine acetylations in the core. A connection to transcription regulation in-vivo is made.