TY - JOUR
T1 - An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency
AU - Ho, Lena
AU - Ronan, Jehnna L.
AU - Wu, Jiang
AU - Staahl, Brett T.
AU - Chen, Lei
AU - Kuo, Ann
AU - Lessard, Julie
AU - Nesvizhskii, Alexey I.
AU - Ranish, Jeff
AU - Crabtree, Gerald R.
PY - 2009/3/31
Y1 - 2009/3/31
N2 - 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.
AB - 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.
KW - BAF complexes
KW - BAF155
KW - Brg
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UR - http://www.scopus.com/inward/citedby.url?scp=65249180173&partnerID=8YFLogxK
U2 - 10.1073/pnas.0812889106
DO - 10.1073/pnas.0812889106
M3 - Article
C2 - 19279220
AN - SCOPUS:65249180173
SN - 0027-8424
VL - 106
SP - 5181
EP - 5186
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -