Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers
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.
Authors
- Arpita Upadhyaya (ORCID: https://orcid.org/0000-0003-1496-919X)
- Kaustubh Wagh (ORCID: https://orcid.org/0000-0001-8514-027X)
- Alba Jiménez‐Panizo (ORCID: https://orcid.org/0000-0001-7046-6162)
- Michelle Lion
- Juan Fernández‐Recio (ORCID: https://orcid.org/0000-0002-3986-7686)
- Gordon L. Hager (ORCID: https://orcid.org/0000-0002-9300-5331)
- David A. Ball (ORCID: https://orcid.org/0000-0002-3976-3668)
- Grégory Fettweis (ORCID: https://orcid.org/0000-0002-6623-2264)
- Manan Krishnamurthy (ORCID: https://orcid.org/0000-0001-8906-0533)
- Sohyoung Kim (ORCID: https://orcid.org/0000-0002-6140-7918)
- Andrea Alegre‐Martí (ORCID: https://orcid.org/0000-0001-6646-8798)
- Didier Vertommen (ORCID: https://orcid.org/0000-0001-7648-8282)
- Tatiana Karpova (ORCID: https://orcid.org/0000-0001-6025-2128)
- Thomas A. Johnson (ORCID: https://orcid.org/0000-0002-9135-3252)
- Eva Estébanez‐Perpiñá (ORCID: https://orcid.org/0000-0003-2687-5801)
- Lorenzo Rinaldi (ORCID: https://orcid.org/0000-0003-2977-4205)
- Diana A. Stavreva (ORCID: https://orcid.org/0000-0002-7904-6452)
- Samuel Dequiedt (ORCID: https://orcid.org/0000-0003-1234-7477)
- Li Wang (ORCID: https://orcid.org/0000-0002-8969-7427)
- Éric Gilson (ORCID: https://orcid.org/0000-0001-5738-6723)
Institutions
- National Institutes of Health (US)
- University of Liège (BE)
- Universidad de La Rioja (ES)
- Instituto de Ciencias de la Vid y del Vino (ES)
- de Duve Institute (BE)
- National Cancer Institute (US)
- Gobierno de La Rioja (ES)
- University of Maryland, College Park (US)
- Universitat de Barcelona (ES)
- UCLouvain (BE)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-05-10
- DOI
- https://doi.org/10.1093/nar/gkaf415
- Citations
- 4
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Science Foundation
- Ministerio de Economía y Competitividad
- National Institutes of Health
- Agencia Estatal de Investigación
- National Cancer Institute
- National Institute of General Medical Sciences