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Updated: Jun 23, 2025
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In Vitro Characterization of Histone Chaperones using Analytical, Pull-Down and Chaperoning Assays
Published on: December 29, 2021
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Structure of the Hir histone chaperone complex.
Hee Jong Kim1, Mary R Szurgot1, Trevor van Eeuwen1
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Molecular Cell
|June 26, 2024
Summary
The Hir/Asf1 chaperone complex structure reveals how it deposits histone tetramers for DNA replication-independent chromatin assembly. This finding clarifies the molecular mechanism of histone chaperone-mediated chromatin formation.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- The HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone are crucial for replication-independent chromatin assembly.
- The molecular architecture and histone deposition mechanism of the HIRA/Hir complex were previously unknown.
Purpose of the Study:
- To determine the molecular architecture of the S. cerevisiae Hir complex in association with Asf1/H3/H4.
- To elucidate the mechanism of histone tetramer deposition mediated by the Hir/Asf1 complex.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the structure.
- High-resolution structural analysis was performed at 2.9-6.8 Å.
Main Results:
- The Hir complex forms an arc-shaped dimer (Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4).
- A central cavity accommodates Asf1/H3/H4, positioned for histone tetramer binding.
- Hir3 C-terminal segments exhibit nucleic acid binding activity for DNA wrapping.
Conclusions:
- The structure provides a model for Hir/Asf1-mediated histone tetramer formation and deposition.
- This work clarifies the mechanism of histone chaperone-assisted chromatin assembly.
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