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bioRxiv · 10.1101/2024.07.10.602876

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

Jeong, T.-K.·Frater, R. C. M.·Groth, A.·Song, J.-J.
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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 electron microscopy (cryo-EM) structure of a human CODANIN-1_ASF1A complex at 3.75 [A] 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 a unique negative regulator that highjacks ASF1 interaction sites with histones and downstream chaperones to inhibit nucleosome assembly.

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Jeong, T.-K., Frater, R. C. M., Groth, A., Song, J.-J.. 2024-07-13. CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate histone supply. https://doi.org/10.1101/2024.07.10.602876

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