Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月4日

查看全文
  • Tae-Kyeong Jeong,
  • R. Ciaran MacKenzie Frater,
  • Jongha Yoon,
  • Anja Groth,
  • Ji-Joon Song

摘要

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.