An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency.
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.
Ho
Lena
L
Program in Immunology, Stanford University, Stanford, CA, USA.
Ronan
Jehnna L
JL
Wu
Jiang
J
Staahl
Brett T
BT
Chen
Lei
L
Kuo
Ann
A
Lessard
Julie
J
Nesvizhskii
Alexey I
AI
Ranish
Jeff
J
Crabtree
Gerald R
GR
D000818:Animals; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D009124:Muscle Proteins / Q000032:analysis; D039904:Pluripotent Stem Cells / Q000166:cytology*; D040901:Proteomics; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D009124:Muscle Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; C491090:Smarcc1 protein, mouse; C529549:Smarcd1 protein, mouse; C494055:Smarcd3 protein, mouse; D014157:Transcription Factors