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

TLDR

SWI/SNF (BAF) chromatin remodeling complexes are essential for totipotent and pluripotent cell formation and are implicated in nuclear reprogramming, yet their precise roles remain unclear. The study demonstrates that BAF complexes are necessary for mouse embryonic stem cell self‑renewal and pluripotency, but not for proliferation of fibroblasts or other cell types. Proteomic analysis identified a distinct esBAF complex (Brg, BAF155, BAF60A) lacking Brm, BAF170, and BAF60C, which is essential for ES cell maintenance and pluripotency and directly interacts with core pluripotency regulators.

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 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.