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

Lena Ho, Jehnna L. Ronan, Jiang Wu, Brett T. Staahl, Lei Chen, Ann Kuo, Julie Lessard, Alexey I. Nesvizhskii, Jeff Ranish, Gerald R. Crabtree

Research output: Contribution to journalArticle

342 Scopus citations

Abstract

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 inscreens for genes required for nuclear reprogramming in Xenopus 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.

Original languageEnglish (US)
Pages (from-to)5181-5186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number13
DOIs
StatePublished - Mar 31 2009

Keywords

  • BAF complexes
  • BAF155
  • Brg

ASJC Scopus subject areas

  • General

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