Is the H4 histone tail intrinsically disordered or intrinsically multifunctional?

Area of Science:

• Biochemistry
• Structural Biology
• Genetics

Background:

• Histone tails are crucial for chromatin organization and genomic information storage.
• Their structural versatility, while essential, poses challenges for experimental and computational analysis.

Purpose of the Study:

• To explore the potential and free energy landscape of isolated and bound H4 histone tails.
• To understand the relationship between histone tail structure, energy landscape, and chromatin organization.

Main Methods:

• Computational analysis of potential and free energy landscapes.
• Investigation of structural ensembles and energy barriers.

Main Results:

• The H4 histone tail's energy landscape shows distinct structural ensembles separated by high energy barriers.
• Little difference was observed between isolated and bound H4 histone tails.
• This landscape facilitates transient interactions essential for liquid-like chromatin organization.

Conclusions:

• The multifunnel energy landscape suggests histone tails possess multifunctionality.
• This landscape may indicate a conformational selection-based binding mechanism.
• Histone tail disorder is better understood within the context of multifunctionality.