An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency

DOI Web Site 被引用文献14件
  • Lena Ho
    Program in Immunology,
  • Jehnna L. Ronan
    Program in Cancer Biology,
  • Jiang Wu
    Howard Hughes Medical Institute and the Departments of Pathology and of Developmental Biology, and
  • Brett T. Staahl
    Program in Developmental Biology, Stanford University, Stanford, CA;
  • Lei Chen
    Howard Hughes Medical Institute and the Departments of Pathology and of Developmental Biology, and
  • Ann Kuo
    Howard Hughes Medical Institute and the Departments of Pathology and of Developmental Biology, and
  • Julie Lessard
    Howard Hughes Medical Institute and the Departments of Pathology and of Developmental Biology, and
  • Alexey I. Nesvizhskii
    University of Michigan, Department of Pathology and Center for Computational Medicine and Biology, Ann Arbor, MI; and
  • Jeff Ranish
    Institute of Systems Biology, Seattle, WA
  • Gerald R. Crabtree
    Howard Hughes Medical Institute and the Departments of Pathology and of Developmental Biology, and

説明

<jats:p> Mammalian SWI/SNF [also called BAF (Brg/Brahma-associated factors)] ATP-dependent chromatin remodeling complexes are essential for formation of the totipotent and pluripotent cells of the early embryo. In addition, subunits of this complex have been recovered in screens for genes required for nuclear reprogramming in <jats:italic>Xenopus</jats:italic> and mouse embryonic stem cell (ES) morphology. However, the mechanism underlying the roles of these complexes is unclear. Here, we show that BAF complexes are required for the self-renewal and pluripotency of mouse ES cells but not for the proliferation of fibroblasts or other cells. Proteomic studies reveal that ES cells express distinctive complexes (esBAF) defined by the presence of Brg (Brahma-related gene), BAF155, and BAF60A, and the absence of Brm (Brahma), BAF170, and BAF60C. We show that this specialized subunit composition is required for ES cell maintenance and pluripotency. Our proteomic analysis also reveals that esBAF complexes interact directly with key regulators of pluripotency, suggesting that esBAF complexes are specialized to interact with ES cell-specific regulators, providing a potential explanation for the requirement of BAF complexes in pluripotency. </jats:p>

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