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<p>Activation of gene transcription is a tightly coordinated process that requires the engagement of transcription factors (TFs) and chromatin remodelers, yet how these components integrate at specific genomic loci remains unclear. Here, we report that ARID1A, a key subunit of the chromatin remodeler cBAF complex, forms condensates through uniformly distributed tyrosine residues within its core intrinsically disordered region (IDR). A series of TFs which feature in the presence of tyrosine within their transcription activation domain (TAD), selectively interact with ARID1A through core IDR-TAD interaction, thereby enabling co-condensation at specific loci. Furthermore, we demonstrate that co-condensation between ARID1A and TFs, such as GATA2, is crucial for maintaining chromatin accessibility and activating genes essential for lung cancer cell proliferation. Collectively, our study establishes the essential role of ARID1A in spatial organization of TFs and cBAF through phase separation, and demonstrates that tyrosine-mediated selective TFs-cBAF co-condensation represents a pivotal mechanism for gene activation.</p>

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Co-condensation between transcription factor and cBAF selectively modulates chromatin remodeling and gene expression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月11日

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  • Xifu Ye,
  • Lin Xu,
  • Xuejiao Sun,
  • Yanzhi Gai,
  • Haixia Yang,
  • Qiang Sun,
  • Jiayi Song,
  • Peiqi Huang,
  • Qianru Zhou,
  • Yaxu Li,
  • Na Li,
  • Jiali Jin,
  • Yang Li,
  • Wei Rao,
  • Huasong Lu,
  • Ping Wang,
  • Chunmei Chang,
  • Yi Lu

摘要

Activation of gene transcription is a tightly coordinated process that requires the engagement of transcription factors (TFs) and chromatin remodelers, yet how these components integrate at specific genomic loci remains unclear. Here, we report that ARID1A, a key subunit of the chromatin remodeler cBAF complex, forms condensates through uniformly distributed tyrosine residues within its core intrinsically disordered region (IDR). A series of TFs which feature in the presence of tyrosine within their transcription activation domain (TAD), selectively interact with ARID1A through core IDR-TAD interaction, thereby enabling co-condensation at specific loci. Furthermore, we demonstrate that co-condensation between ARID1A and TFs, such as GATA2, is crucial for maintaining chromatin accessibility and activating genes essential for lung cancer cell proliferation. Collectively, our study establishes the essential role of ARID1A in spatial organization of TFs and cBAF through phase separation, and demonstrates that tyrosine-mediated selective TFs-cBAF co-condensation represents a pivotal mechanism for gene activation.