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<p>Chromatin remodelers are vital for cellular functions like transcription by modulating nucleosome accessibility. Although biological condensates regulate these processes, the contribution of chromatin remodelers to condensation mechanisms remains poorly understood. Here, we examine the role of the E1321 frameshift mutation in <i>CHD1</i>, a chromatin remodeler, which is often targeted in cancers. This mutation truncates CHD1’s C-terminus, leading to an oncogenic transcriptome and promoting tumorigenesis. This is due to the loss of an intrinsically disordered region (IDR) crucial for forming CHD1 condensates. These condensates are facilitated by the presence of H3K4me3-modified nucleosomes and RNA, guided to active promoters to regulate gene expression. Furthermore, CHD1 condensates contain long noncoding RNA and histone-modifying proteins, revealing an integral role for CHD1 condensates in epigenetic regulation. Among these components, <i>MLL</i> mutations frequently co-occur with <i>CHD1</i> mutations in various cancers, suggesting a shared pathway in cancer development. These findings underscore the importance of chromatin remodeler condensation as a regulatory hub in various cellular processes and tumor suppression.</p>

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Condensation-dependent interactome of a chromatin remodeler underlies tumor suppressor activities

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月30日

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  • Yasuhiro Tsukamoto,
  • Atsuki Kawamura,
  • Ayhan Yurtsever,
  • Hidefumi Suzuki,
  • Nichole Marcela Rojas-Chaverra,
  • Hiroki Sato,
  • Daisuke Ino,
  • Takehiko Ichikawa,
  • Weilin Wei,
  • Shojiro Haji,
  • Dominic Chih-Cheng Voon,
  • Akinobu Matsumoto,
  • Kunio Matsumoto,
  • Hidehisa Takahashi,
  • Noriyuki Kodera,
  • Takeshi Fukuma,
  • Yoshihiro Ogawa,
  • Masaaki Nishiyama,
  • Katsuya Sakai

摘要

Chromatin remodelers are vital for cellular functions like transcription by modulating nucleosome accessibility. Although biological condensates regulate these processes, the contribution of chromatin remodelers to condensation mechanisms remains poorly understood. Here, we examine the role of the E1321 frameshift mutation in CHD1, a chromatin remodeler, which is often targeted in cancers. This mutation truncates CHD1’s C-terminus, leading to an oncogenic transcriptome and promoting tumorigenesis. This is due to the loss of an intrinsically disordered region (IDR) crucial for forming CHD1 condensates. These condensates are facilitated by the presence of H3K4me3-modified nucleosomes and RNA, guided to active promoters to regulate gene expression. Furthermore, CHD1 condensates contain long noncoding RNA and histone-modifying proteins, revealing an integral role for CHD1 condensates in epigenetic regulation. Among these components, MLL mutations frequently co-occur with CHD1 mutations in various cancers, suggesting a shared pathway in cancer development. These findings underscore the importance of chromatin remodeler condensation as a regulatory hub in various cellular processes and tumor suppression.