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A disordered region controls cBAF activity via condensation and partner recruitment.
Patil, Ajinkya; Strom, Amy R; Paulo, Joao A; Collings, Clayton K; Ruff, Kiersten M; Shinn, Min Kyung; Sankar, Akshay; Cervantes, Kasey S; Wauer, Tobias; St Laurent, Jessica D; Xu, Grace; Becker, Lindsay A; Gygi, Steven P; Pappu, Rohit V; Brangwynne, Clifford P; Kadoch, Cigall.
Afiliação
  • Patil A; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
  • Strom AR; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
  • Paulo JA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Collings CK; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ruff KM; Department of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Shinn MK; Department of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Sankar A; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Cervantes KS; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wauer T; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
  • St Laurent JD; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Xu G; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Becker LA; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
  • Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Pappu RV; Department of Biomedical Engineering and Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63130, USA.
  • Brangwynne CP; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Howard Hughes Medical Institute, Chevy Chase, MD 21044, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA. Electronic address: cbrangwy@princeton.edu.
  • Kadoch C; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 21044, USA. Electronic address: cigall_kadoch@dfci.harvard.edu.
Cell ; 186(22): 4936-4955.e26, 2023 10 26.
Article em En | MEDLINE | ID: mdl-37788668
ABSTRACT
Intrinsically disordered regions (IDRs) represent a large percentage of overall nuclear protein content. The prevailing dogma is that IDRs engage in non-specific interactions because they are poorly constrained by evolutionary selection. Here, we demonstrate that condensate formation and heterotypic interactions are distinct and separable features of an IDR within the ARID1A/B subunits of the mSWI/SNF chromatin remodeler, cBAF, and establish distinct "sequence grammars" underlying each contribution. Condensation is driven by uniformly distributed tyrosine residues, and partner interactions are mediated by non-random blocks rich in alanine, glycine, and glutamine residues. These features concentrate a specific cBAF protein-protein interaction network and are essential for chromatin localization and activity. Importantly, human disease-associated perturbations in ARID1B IDR sequence grammars disrupt cBAF function in cells. Together, these data identify IDR contributions to chromatin remodeling and explain how phase separation provides a mechanism through which both genomic localization and functional partner recruitment are achieved.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Montagem e Desmontagem da Cromatina / Complexos Multiproteicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Montagem e Desmontagem da Cromatina / Complexos Multiproteicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos