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Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes.
Mashtalir, Nazar; D'Avino, Andrew R; Michel, Brittany C; Luo, Jie; Pan, Joshua; Otto, Jordan E; Zullow, Hayley J; McKenzie, Zachary M; Kubiak, Rachel L; St Pierre, Roodolph; Valencia, Alfredo M; Poynter, Steven J; Cassel, Seth H; Ranish, Jeffrey A; Kadoch, Cigall.
Affiliation
  • Mashtalir N; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • D'Avino AR; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Michel BC; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Biological and Biomedical Sciences Graduate Program, Harvard Medical School, Boston, MA 02215, USA.
  • Luo J; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Pan J; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Biological and Biomedical Sciences Graduate Program, Harvard Medical School, Boston, MA 02215, USA.
  • Otto JE; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology Program, Harvard University, Cambridge, MA 02138, USA.
  • Zullow HJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Biological and Biomedical Sciences Graduate Program, Harvard Medical School, Boston, MA 02215, USA.
  • McKenzie ZM; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Kubiak RL; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • St Pierre R; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology Program, Harvard University, Cambridge, MA 02138, USA.
  • Valencia AM; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology Program, Harvard University, Cambridge, MA 02138, USA.
  • Poynter SJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology Program, Harvard University, Cambridge, MA 02138, USA.
  • Cassel SH; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Biological and Biomedical Sciences Graduate Program, Harvard Medical School, Boston, MA 02215, USA.
  • Ranish JA; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Kadoch C; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: cigall_kadoch@dfci.harvard.edu.
Cell ; 175(5): 1272-1288.e20, 2018 11 15.
Article in En | MEDLINE | ID: mdl-30343899
ABSTRACT
Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes are multi-subunit molecular machines that play vital roles in regulating genomic architecture and are frequently disrupted in human cancer and developmental disorders. To date, the modular organization and pathways of assembly of these chromatin regulators remain unknown, presenting a major barrier to structural and functional determination. Here, we elucidate the architecture and assembly pathway across three classes of mSWI/SNF complexes-canonical BRG1/BRM-associated factor (BAF), polybromo-associated BAF (PBAF), and newly defined ncBAF complexes-and define the requirement of each subunit for complex formation and stability. Using affinity purification of endogenous complexes from mammalian and Drosophila cells coupled with cross-linking mass spectrometry (CX-MS) and mutagenesis, we uncover three distinct and evolutionarily conserved modules, their organization, and the temporal incorporation of these modules into each complete mSWI/SNF complex class. Finally, we map human disease-associated mutations within subunits and modules, defining specific topological regions that are affected upon subunit perturbation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Chromatin / Chromosomal Proteins, Non-Histone / Chromatin Assembly and Disassembly Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Cell Year: 2018 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Chromatin / Chromosomal Proteins, Non-Histone / Chromatin Assembly and Disassembly Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Cell Year: 2018 Document type: Article Affiliation country: