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

L Ho, JL Ronan, J Wu, BT Staahl… - Proceedings of the …, 2009 - National Acad Sciences
L Ho, JL Ronan, J Wu, BT Staahl, L Chen, A Kuo, J Lessard, AI Nesvizhskii, J Ranish
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
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 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 …
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 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.
National Acad Sciences