Structure of the Hir histone chaperone complex

Hee Jong Kim; Mary R. Szurgot; Trevor van Eeuwen; M. Daniel Ricketts; Pratik Basnet; Athena L. Zhang; Austin Vogt; Samah Sharmin; Craig D. Kaplan; Benjamin A. Garcia; Ronen Marmorstein; Kenji Murakami

doi:10.1016/j.molcel.2024.05.031

Structure of the Hir histone chaperone complex

Hee Jong Kim, Mary R. Szurgot, Trevor van Eeuwen, M. Daniel Ricketts, Pratik Basnet, Athena L. Zhang, Austin Vogt, Samah Sharmin, Craig D. Kaplan, Benjamin A. Garcia, Ronen Marmorstein, Kenji Murakami

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)₂ tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9–6.8 Å resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4)₂ tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.

Original language	English
Pages (from-to)	2601-2617.e12
Journal	Molecular cell
Volume	84
Issue number	14
DOIs	https://doi.org/10.1016/j.molcel.2024.05.031
State	Published - Jul 25 2024

Keywords

Asf1
H3/H4
HIRA
Hir
chromatin
crosslinking mass spectrometry
cryo-electron microscopy
histone chaperone
nucleosome
transcription

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10.1016/j.molcel.2024.05.031

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title = "Structure of the Hir histone chaperone complex",

abstract = "The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)2 tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9–6.8 {\AA} resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4)2 tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.",

keywords = "Asf1, H3/H4, HIRA, Hir, chromatin, crosslinking mass spectrometry, cryo-electron microscopy, histone chaperone, nucleosome, transcription",

author = "Kim, {Hee Jong} and Szurgot, {Mary R.} and {van Eeuwen}, Trevor and Ricketts, {M. Daniel} and Pratik Basnet and Zhang, {Athena L.} and Austin Vogt and Samah Sharmin and Kaplan, {Craig D.} and Garcia, {Benjamin A.} and Ronen Marmorstein and Kenji Murakami",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = jul,

day = "25",

doi = "10.1016/j.molcel.2024.05.031",

language = "English",

volume = "84",

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AU - Kim, Hee Jong

AU - Szurgot, Mary R.

AU - van Eeuwen, Trevor

AU - Ricketts, M. Daniel

AU - Basnet, Pratik

AU - Zhang, Athena L.

AU - Vogt, Austin

AU - Sharmin, Samah

AU - Kaplan, Craig D.

AU - Garcia, Benjamin A.

AU - Marmorstein, Ronen

AU - Murakami, Kenji

PY - 2024/7/25

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N2 - The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)2 tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9–6.8 Å resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4)2 tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.

AB - The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit histone (H3/H4)2 tetramers on DNA for replication-independent chromatin assembly. The molecular architecture of the HIRA/Hir complex and its mode of histone deposition have remained unknown. Here, we report the cryo-EM structure of the S. cerevisiae Hir complex with Asf1/H3/H4 at 2.9–6.8 Å resolution. We find that the Hir complex forms an arc-shaped dimer with a Hir1/Hir2/Hir3/Hpc2 stoichiometry of 2/4/2/4. The core of the complex containing two Hir1/Hir2/Hir2 trimers and N-terminal segments of Hir3 forms a central cavity containing two copies of Hpc2, with one engaged by Asf1/H3/H4, in a suitable position to accommodate a histone (H3/H4)2 tetramer, while the C-terminal segments of Hir3 harbor nucleic acid binding activity to wrap DNA around the Hpc2-assisted histone tetramer. The structure suggests a model for how the Hir/Asf1 complex promotes the formation of histone tetramers for their subsequent deposition onto DNA.

KW - Asf1

KW - H3/H4

KW - HIRA

KW - Hir

KW - chromatin

KW - crosslinking mass spectrometry

KW - cryo-electron microscopy

KW - histone chaperone

KW - nucleosome

KW - transcription

UR - http://www.scopus.com/inward/record.url?scp=85198344997&partnerID=8YFLogxK

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DO - 10.1016/j.molcel.2024.05.031

M3 - Article

C2 - 38925115

AN - SCOPUS:85198344997

SN - 1097-2765

VL - 84

SP - 2601-2617.e12

JO - Molecular cell

JF - Molecular cell

IS - 14

ER -

Structure of the Hir histone chaperone complex

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Keywords

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