Contributors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Institut de Biologie Intégrative de la Cellule (I2BC); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS); European Molecular Biology Laboratory Heidelberg (EMBL); European Molecular Biology Laboratory Hamburg (EMBL); Architecture et Réactivité de l'ARN (ARN); Institut de biologie moléculaire et cellulaire (IBMC); Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS); Institute of Molecular Systems Biology Zurich; Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology Zürich (ETH Zürich); University of Ottawa Ottawa; Ottawa Institute of Systems Biology; ANR-23-CE11-0002,SWING,Structure et fonction des nouvelles sous-unités SWI/SNF dans la réponse aux dommages de l'ADN(2023); ANR-24-CE12-1416,BAF-NER,Les complexes cBAF, PBAF et ncBAF en action : Comprendre leur rôle dans la réparation par excision de nucléotides(2024); ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010); ANR-21-ESRE-0046,France-Cryo-EM,National instrumentation in cryo electron microscopy(2021)
نبذة مختصرة : International audience ; 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 comple x. T heir function in the complex is unkno wn, and v ery limited str uct ural information is available, despite the fact that they are mutated in several cancer types, most notably blood malignancies and hence medically rele v ant. Here, using cry o-electron microscop y in combination with bioph y sical and bioc hemical approac hes, w e sho w that BCL7A forms a st able, high-affinit y 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 str uct ural 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.
Processing Request
No Comments.