CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply
Year: 2025
Type: article
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.
Source: Nature Communications
Authors: Tae-Kyeong Jeong, R. Ciaran MacKenzie Frater, Jongha Yoon, Anja Groth, Ji-Joon Song
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Research Foundation, Korea Institute of Science and Technology, Korea Institute of Science and Technology Information, National Research Foundation of Korea, Novo Nordisk, Korea Advanced Institute of Science and Technology, Novo Nordisk Fonden, Korea Research Environment Open Network, Great Southern Development Commission, Government of Western Australia
OpenAlex ID: W4408149786