Unraveling the mystery of histone tail function in nucleosome unwinding
Unraveling the mystery of histone tail function in nucleosome unwinding lead image
Histone proteins act as spools as they tightly wind chromatin, a complex composed of DNA, RNA and protein, like balls of string, around themselves to turn the DNA material into nucleosomes.
Scientists have known that the tails of histone proteins play a crucial role in maintaining nucleosome particle stability and adjusting its compactness necessary for genome function, but a deeper understanding of how this balancing act occurs remains elusive.
Parsons and Zhang provided a new step forward in unraveling this mystery. By focusing on the physics of the spooling process, including the interactions between the negatively charged DNA and positively charged protein tails and the geometry of the nucleosome layers, the researchers successfully calculated the free-energy profile of a single nucleosome.
Using a chemically accurate, near atomistic protein-DNA model, the researchers determined the free-energy profile for unwinding both the inner and outer DNA layers, which are formed by the complicated twisting pattern during nucleosome wrapping.
Results from their simulations identified a large energetic barrier that decouples the outer and inner DNA unwinding into two separate processes occurring on different timescales. This decoupling ensures the stability of the nucleosome as the outer DNA unwraps to promote its accessibility and genome function.
The research suggests that the transition barrier has a strong chemical origin and mainly arises from a delayed loss of histone tail contact with the DNA.
“Strikingly, this loss of contact mobilizes the disordered tails and leads to a significant increase of entropy that favors nucleosome unwinding,” Zhang said.
Their results suggest that histone modifications could be used to regulate nucleosome stability by fine-tuning the entropy of disordered tails.
Source: “Critical role of histone tail entropy in nucleosome unwinding,” by Thomas Parsons and Bin Zhang, The Journal of Chemical Physics (2019). The article can be accessed at https://doi.org/10.1063/1.5085663 .
