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<p>ATP-dependent chromatin remodellers are specialized multiprotein machines that organize the genome in eukaryotic cells and regulate its accessibility by repositioning, ejecting or modifying nucleosomes. However, their role in <i>Toxoplasma gondii</i> is poorly understood. Here we show that <i>T.</i> <i>gondii</i> has evolved two divergent proteins within the imitation switch (ISWI) family: <i>Tg</i>SNF2h and <i>Tg</i>SNF2L. <i>Tg</i>SNF2h specifically forms a core complex with the transcription factor AP2VIII-2 and the scaffold protein <i>Tg</i>RFTS. Depletion of <i>Tg</i>RFTS phenocopies the knockdown of <i>Tg</i>SNF2h, restricting access to chromatin and altering local gene expression. At the genomic level, <i>Tg</i>SNF2h insulates highly transcribed genes from silenced neighbours, ensuring stage-specific gene regulation. By modulating chromatin accessibility to transcription factors, <i>Tg</i>SNF2h exerts epistatic control over MORC, a key regulator of sexual commitment. Our findings show that a specific ISWI complex orchestrates the partitioning of developmental genes and ensures transcriptional fidelity throughout the parasite life cycle.</p>

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An ISWI-related chromatin remodeller regulates stage-specific gene expression in Toxoplasma gondii

  • 期刊论文

  • 发表日期：

    2025年4月11日

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  • Belen Pachano,
  • Dayana C. Farhat,
  • Martina Shahinas,
  • Jill von Velsen,
  • Charlotte Corrao,
  • Lucid Belmudes,
  • Pieter-Jan de Bock,
  • Caroline Mas,
  • Yohann Couté,
  • Matthew W. Bowler,
  • Alexandre Bougdour,
  • Christopher Swale,
  • Mohamed-Ali Hakimi

摘要

ATP-dependent chromatin remodellers are specialized multiprotein machines that organize the genome in eukaryotic cells and regulate its accessibility by repositioning, ejecting or modifying nucleosomes. However, their role in Toxoplasma gondii is poorly understood. Here we show that T. gondii has evolved two divergent proteins within the imitation switch (ISWI) family: TgSNF2h and TgSNF2L. TgSNF2h specifically forms a core complex with the transcription factor AP2VIII-2 and the scaffold protein TgRFTS. Depletion of TgRFTS phenocopies the knockdown of TgSNF2h, restricting access to chromatin and altering local gene expression. At the genomic level, TgSNF2h insulates highly transcribed genes from silenced neighbours, ensuring stage-specific gene regulation. By modulating chromatin accessibility to transcription factors, TgSNF2h exerts epistatic control over MORC, a key regulator of sexual commitment. Our findings show that a specific ISWI complex orchestrates the partitioning of developmental genes and ensures transcriptional fidelity throughout the parasite life cycle.