Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers

  1. Gregory Fettweis
  2. Kaustubh Wagh
  3. Diana A Stavreva
  4. Alba Jiménez-Panizo
  5. Sohyoung Kim
  6. Michelle Lion
  7. Andrea Alegre-Martí
  8. Lorenzo Rinaldi
  9. Thomas A Johnson
  10. Elise Gilson
  11. Manan Krishnamurthy
  12. Li Wang
  13. David A Ball
  14. Tatiana S Karpova
  15. Arpita Upadhyaya
  16. Didier Vertommen
  17. Juan Fernández Recio
  18. Eva Estébanez-Perpiñá
  19. Franck Dequiedt
  20. Gordon L Hager
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Abstract

While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not understood. Recently, we and others have proposed that direct interactions with transcription factors lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of LxxLL motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs. One of these clusters interacts with MAU2 and is necessary for the maintenance of the NIPBL–MAU2 heterodimer. The second cluster binds specifically to the ligand-binding domains of steroid receptors. For the glucocorticoid receptor (GR), we examine in detail its interaction surfaces with NIPBL and MAU2. Using AlphaFold2 and molecular docking algorithms, we uncover a GR–NIPBL–MAU2 ternary complex and describe its importance in GR-dependent gene regulation. Finally, we show that multiple transcription factors interact with NIPBL–MAU2, likely using interfaces other than those characterized for GR.

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  1. Version published to 10.1093/nar/gkaf415
  2. Mentioned by @rridrobot.bsky.social on Bluesky

    A preprint using: pCDNA 3 5' cMyc SMC1 (RRID:Addgene_32363) from #Addgene was published. SciScore made a table with this resource, see “Automated Services” module (download as csv, xml or #jats) #methodsmatter #reproducibility

  3. Mentioned by @alexis-verger.cpesr.fr on Bluesky

    Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers www.biorxiv.org/content/10.1...

  4. Mentioned by @aixbiobot.bsky.social on Bluesky

    Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers [updated] GR-like TFs form complex w/ NIPBL/MAU2. NIPBL LxxLL drives cohesin/enhancer, gene reg.

  5. Version published to 10.1101/2024.12.09.627537v2 on bioRxiv
  6. Mentioned by @estebanezlab.bsky.social on Bluesky

    🎯 Cohesin complex is a key player in genome architecture but how localizes to specific chromatin sites is not understood. We identified two LxxL motifs in NIPBL regulating its dynamics, interactome & dependent transcriptional programs. New article in collaboration: www.biorxiv.org/content/10.1...

  7. Mentioned by @biorxiv-molbio.bsky.social on Bluesky

    Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers https://www.biorxiv.org/content/10.1101/2024.12.09.627537v1

  8. Mentioned by @biorxivpreprint.bsky.social on Bluesky

    Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers https://www.biorxiv.org/content/10.1101/2024.12.09.627537v1

  9. Version published to 10.1101/2024.12.09.627537v1 on bioRxiv