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

Author

Listed:
  • Tae-Kyeong Jeong

    (Korea Advanced Institute of Science and Technology (KAIST))

  • R. Ciaran MacKenzie Frater

    (University of Copenhagen)

  • Jongha Yoon

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Anja Groth

    (University of Copenhagen
    University of Copenhagen
    University of Copenhagen)

  • Ji-Joon Song

    (Korea Advanced Institute of Science and Technology (KAIST))

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.

Suggested Citation

  • Tae-Kyeong Jeong & R. Ciaran MacKenzie Frater & Jongha Yoon & Anja Groth & Ji-Joon Song, 2025. "CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56976-7
    DOI: 10.1038/s41467-025-56976-7
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