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Cited by 8Genomics and Chromatin DynamicsNuclear Structure and FunctionProtein Structure and Dynamics

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CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply

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Jeong, Tae-Kyeong, Frater, R. Ciaran MacKenzie, Yoon, Jongha, Groth, Anja, Song, Ji-Joon·2025·Nature Communications
DOI 10.1038/s41467-025-56976-7PMC PMC11880193

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Abstract

ASF1 is a major histone chaperone that regulates the supply of histone H3–H4 and facilitates nucleosome assembly to maintain chromatin structure during DNA replication and transcription. CODANIN-1 negatively regulates the function of ASF1. However, the molecular mechanism by which CODANIN-1 inhibits the ASF1-mediated histone supply remains elusive. Here, we present the cryo-EM structure of a human CODANIN-1_ASF1A complex at 3.75 Å resolution. The structure reveals that CODANIN-1 forms a dimer where each monomer holds two ASF1 molecules, utilizing two B-domains and two histone H3 mimic helices (HMHs). The interaction of CODANIN-1 with ASF1 via the HMH and B-domains inhibits the formation of an ASF1/H3–H4 complex and sequesters ASF1 in the cytoplasm. Our study provides a structural and molecular basis for the function of CODANIN-1 as negative regulator that highjacks ASF1 interaction sites with histones and downstream chaperones to inhibit nucleosome assembly. CODANIN-1 negatively regulates the function of ASF1, the key chaperone for histone H3-H4 supply. Here the authors present the cryo-EM structure of the CODANIN-1_ASF1A complex, showing that CODANIN-1 utilizes histone H3-mimic helices and B-domains to sequester ASF1A, thereby inhibiting ASF1 function.

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Metadata

Authors
Jeong, T.-K., Frater, R. C. M., Yoon, J., Groth, A., & Song, J.-J.
Affiliations
  • Korea Advanced Institute of Science and Technology (KR)
  • University of Copenhagen (DK)
Corresponding author
  • Groth, Anja
  • Song, Ji-Joon
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-03-04
Volume
16
Issue
1
Pages
2181-2181
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-56976-7
PMC
PMC11880193
OpenAlex
W4408149786
Cited by
8
References
3
Citations by year
2026: 4 · 2025: 2
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation of Korea (RS-2023-00266300, RS-2024-00440614)
  • Novo Nordisk Fonden (NNF21OC0067425, NNF14CC0001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
Asf1, histone chaperone, nucleosome assembly, negative regulation, protein complex structure, B domain, cytoplasmic sequestration, chromatin structure
MeSH terms
Histones, Humans, Models, Molecular, Nucleosomes, Protein Binding, Transcription Factors, Cell Cycle Proteins, Molecular Chaperones, Cryoelectron Microscopy, Protein Multimerization, Histone Chaperones

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