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<p>The protein interactome of p65/RELA, the most active subunit of the transcription factor (TF) NF-κB, has not been previously determined in living cells. Using p65-miniTurbo fusion proteins and biotin tagging, we identify &gt;350 RELA interactors from untreated and IL-1α-stimulated cells, including many TFs (47% of all interactors) and &gt;50 epigenetic regulators belonging to different classes of chromatin remodeling complexes. A comparison with the interactomes of two point mutants of p65 reveals that the interactions primarily require intact dimerization rather than DNA-binding properties. A targeted RNAi screen for 38 interactors and subsequent functional transcriptome and bioinformatics studies identify gene regulatory (sub)networks, each controlled by RELA in combination with one of the TFs ZBTB5, GLIS2, TFE3/TFEB, or S100A8/A9. The large, dynamic and versatile high-resolution interactome of RELA and its gene regulatory logics provides a rich resource and a new framework for explaining how RELA cooperativity determines gene expression patterns.</p>

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The proximity-based protein interactome and regulatory logics of the transcription factor p65 NF-κB/RELA

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月3日

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  • Lisa Leib,
  • Jana Juli,
  • Liane Jurida,
  • Christin Mayr-Buro,
  • Jasmin Priester,
  • Hendrik Weiser,
  • Stefanie Wirth,
  • Simon Hanel,
  • Daniel Heylmann,
  • Axel Weber,
  • M Lienhard Schmitz,
  • Argyris Papantonis,
  • Marek Bartkuhn,
  • Jochen Wilhelm,
  • Uwe Linne,
  • Johanna Meier-Soelch,
  • Michael Kracht

摘要

The protein interactome of p65/RELA, the most active subunit of the transcription factor (TF) NF-κB, has not been previously determined in living cells. Using p65-miniTurbo fusion proteins and biotin tagging, we identify >350 RELA interactors from untreated and IL-1α-stimulated cells, including many TFs (47% of all interactors) and >50 epigenetic regulators belonging to different classes of chromatin remodeling complexes. A comparison with the interactomes of two point mutants of p65 reveals that the interactions primarily require intact dimerization rather than DNA-binding properties. A targeted RNAi screen for 38 interactors and subsequent functional transcriptome and bioinformatics studies identify gene regulatory (sub)networks, each controlled by RELA in combination with one of the TFs ZBTB5, GLIS2, TFE3/TFEB, or S100A8/A9. The large, dynamic and versatile high-resolution interactome of RELA and its gene regulatory logics provides a rich resource and a new framework for explaining how RELA cooperativity determines gene expression patterns.