How to evict HP1 from H3: Using a complex salt bridge

Area of Science:

• Molecular Biology
• Epigenetics
• Structural Biology

Background:

• The histone code hypothesis explains gene silencing and activation through post-translational modifications.
• Heterochromatin Protein 1 (HP1) binds to tri-methylated Lysine9 (K9me3) on histone-H3.
• HP1 is known to be evicted during mitosis upon phosphorylation of Serine10 (S10phos).

Purpose of the Study:

• To elucidate the molecular mechanisms underlying HP1 eviction from histone-H3.
• To detail the atomic interactions driving the "binary switch" in gene regulation.
• To understand the role of Serine10 phosphorylation in HP1 dynamics.

Main Methods:

• Quantum mechanical calculations were employed to model intermolecular interactions.
• Analysis focused on the electrostatic and cation-π interactions between HP1, histone-H3, and associated residues.
• The study investigated the formation of salt bridges involving arginine and S10phos.

Main Results:

• An electrostatic interaction competes with the cation-π interaction, dislodging K9me3 from HP1's aromatic cage.
• An arginine residue forms an intermolecular "complex salt bridge" with S10phos.
• This salt bridge formation facilitates the eviction of HP1.

Conclusions:

• The study provides a detailed atomic-level understanding of HP1 eviction during mitosis.
• Phosphorylation of Serine10 on histone-H3 is a critical trigger for HP1 release.
• These findings offer insights into the dynamic "binary switch" mechanisms of the histone code.