2. Academic Validation
  3. Structure of the nucleosome-bound human BCL7A

Structure of the nucleosome-bound human BCL7A

  • Nucleic Acids Res. 2025 Apr 10;53(7):gkaf273. doi: 10.1093/nar/gkaf273.
Franck Martin 1 2 3 4,  Asgar Abbas Kazrani 1 2 3 4,  Julie Lafouge 1 2 3 4,  Dana Mariel Diaz-Jimenez 1 2 3 4,  Stéphanie Siebert 1 2 3 4,  Leonie Fabbro-Burtschell 1 2 3 4,  Emma Maillard 5,  Karine Lapouge 6,  Haydyn David Thomas Mertens 7,  Claude Sauter 8,  Alexander Leitner 9,  Françoise Ochsenbein 5,  Alexandre Blais 10 11 12 13,  Elisa Bergamin 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Functional Genomics and Cancer & Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch-Graffenstaden, France.
  • 2 Université de Strasbourg, 67084 Strasbourg, France.
  • 3 Centre National de la Recherche Scientifique UMR 7104, 67400 Illkirch-Graffenstaden, France.
  • 4 Institut National de la Santé et de la Recherche Médicale U1258, 67400 Illkirch-Graffenstaden, France.
  • 5 Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 91190 Gif-sur-Yvette, France.
  • 6 Protein Expression and Purification Core Facility, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
  • 7 European Molecular Biology Laboratory (EMBL), Hamburg Outstation, c/o DESY, Notkestraße 85, 22607 Hamburg, Germany.
  • 8 Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 2 All. Konrad Roentgen, 67084 Strasbourg, France.
  • 9 Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland.
  • 10 Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
  • 11 Ottawa Institute of Systems Biology, Ottawa, Ontario K1H 8M5, Canada.
  • 12 University of Ottawa Centre for Inflammation, Immunity and Infection (CI3), Ottawa, Ontario K1H 8M5, Canada.
  • 13 Éric Poulin Centre for Neuromuscular Disease, Ottawa, Ontario K1H 8M5, Canada.
PMID: 40207634 DOI: 10.1093/nar/gkaf273
Abstract

Proteins of the BCL7 family (BCL7A, BCL7B, and BCL7C) are among the most recently identified subunits of the mammalian SWI/SNF chromatin remodeler complex and are absent from the unicellular version of this complex. Their function in the complex is unknown, and very limited structural information is available, despite the fact that they are mutated in several Cancer types, most notably blood malignancies and hence medically relevant. Here, using cryo-electron microscopy in combination with biophysical and biochemical approaches, we show that BCL7A forms a stable, high-affinity complex with the nucleosome core particle (NCP) through binding of BCL7A with the acidic patch of the nucleosome via an arginine anchor motif. This interaction is impaired by BCL7A mutations found in Cancer. Further, we determined that BCL7A contributes to the remodeling activity of the mSWI/SNF complex and we examined its function at the genomic level. Our findings reveal how BCL7 proteins interact with the NCP and help rationalize the impact of cancer-associated mutations. By providing structural information on the positioning of BCL7 on the NCP, our results broaden the understanding of the mechanism by which SWI/SNF recognizes the chromatin fiber.

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