Scholarlink

<p>The Microrchidia (MORC) family of chromatin-remodelling ATPases is pivotal in forming higher-order chromatin structures that suppress transcription. The exact mechanisms of MORC-induced chromatin remodelling have been elusive. Here, we report an in vitro reconstitution of full-length MORC2, the most commonly mutated MORC member, linked to various cancers and neurological disorders. MORC2 possesses multiple DNA-binding sites that undergo structural rearrangement upon DNA binding. MORC2 locks onto the DNA using its C-terminal domain (CTD) and acts as a clamp. A conserved phosphate-interacting motif within the CTD was found to regulate ATP hydrolysis and cooperative DNA binding. Importantly, MORC2 mediates chromatin remodelling via ATP hydrolysis-dependent DNA compaction in vitro, regulated by the phosphorylation state of its CTD. These findings position MORC2 CTD phosphorylation as a critical regulator of chromatin remodelling and a promising therapeutic target.</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

MORC2 is a phosphorylation-dependent DNA compaction machine

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Winnie Tan,
  • Jeongveen Park,
  • Hariprasad Venugopal,
  • Jieqiong Lou,
  • Prabavi Shayana Dias,
  • Pedro L. Baldoni,
  • Kyoung-Wook Moon,
  • Toby A. Dite,
  • Christine R. Keenan,
  • Alexandra D. Gurzau,
  • Joonyoung Lee,
  • Timothy M. Johanson,
  • Andrew Leis,
  • Jumana Yousef,
  • Vineet Vaibhav,
  • Laura F. Dagley,
  • Ching-Seng Ang,
  • Laura D. Corso,
  • Chen Davidovich,
  • Stephin J. Vervoort,
  • Gordon K. Smyth,
  • Marnie E. Blewitt,
  • Rhys S. Allan,
  • Elizabeth Hinde,
  • Sheena D’Arcy,
  • Je-Kyung Ryu,
  • Shabih Shakeel

摘要

The Microrchidia (MORC) family of chromatin-remodelling ATPases is pivotal in forming higher-order chromatin structures that suppress transcription. The exact mechanisms of MORC-induced chromatin remodelling have been elusive. Here, we report an in vitro reconstitution of full-length MORC2, the most commonly mutated MORC member, linked to various cancers and neurological disorders. MORC2 possesses multiple DNA-binding sites that undergo structural rearrangement upon DNA binding. MORC2 locks onto the DNA using its C-terminal domain (CTD) and acts as a clamp. A conserved phosphate-interacting motif within the CTD was found to regulate ATP hydrolysis and cooperative DNA binding. Importantly, MORC2 mediates chromatin remodelling via ATP hydrolysis-dependent DNA compaction in vitro, regulated by the phosphorylation state of its CTD. These findings position MORC2 CTD phosphorylation as a critical regulator of chromatin remodelling and a promising therapeutic target.