PMID:16801560

Citation	Suzuki, A, Raya, A, Kawakami, Y, Morita, M, Matsui, T, Nakashima, K, Gage, FH, Rodríguez-Esteban, C and Izpisúa Belmonte, JC (2006) Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. 103:10294-9
Abstract	ES cells represent a valuable model for investigating early embryo development and hold promise for future regenerative medicine strategies. The self-renewal of pluripotent mouse ES cells has been shown to require extrinsic stimulation by the bone morphogenetic protein (BMP) and leukemia inhibitory factor signaling pathways and the expression of the transcription factors Oct4 and Nanog. However, the network of interactions among extrinsic and intrinsic determinants of ES cell pluripotency is currently poorly understood. Here, we show that Nanog expression is up-regulated in mouse ES cells by the binding of T (Brachyury) and STAT3 to an enhancer element in the mouse Nanog gene. We further show that Nanog blocks BMP-induced mesoderm differentiation of ES cells by physically interacting with Smad1 and interfering with the recruitment of coactivators to the active Smad transcriptional complexes. Taken together, our findings illustrate the existence of ES cell-specific regulatory networks that underlie the maintenance of ES cell pluripotency and provide mechanistic insights into the role of Nanog in this process.
Links	PubMed PMC1502451 Online version:10.1073/pnas.0506945103
Keywords	Animals; Base Sequence; Binding Sites; Bone Morphogenetic Proteins/pharmacology; Cell Differentiation/drug effects; Cells, Cultured; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Down-Regulation; Embryo, Mammalian/cytology; Enhancer Elements, Genetic; Fetal Proteins/genetics; Fetal Proteins/metabolism; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Mesoderm/cytology; Mesoderm/drug effects; Mesoderm/metabolism; Mice; Molecular Sequence Data; Promoter Regions, Genetic/genetics; Protein Binding; STAT Transcription Factors/genetics; STAT Transcription Factors/metabolism; Signal Transduction; Smad1 Protein/metabolism; Stem Cells/cytology; Stem Cells/drug effects; Stem Cells/metabolism; T-Box Domain Proteins/genetics; T-Box Domain Proteins/metabolism
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