title: A membrane-associated β-catenin/Oct4 complex correlates with ground-state pluripotency in mouse embryonic stem cells.
abstract: The maintenance of pluripotency in mouse embryonic stem cells (mESCs) relies on the activity of a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3. Extracellular signals modulate the activity of the network and regulate the differentiation capacity of the cells. Wnt/β-catenin signaling has emerged as a significant potentiator of pluripotency: increases in the levels of β-catenin regulate the activity of Oct4 and Nanog, and enhance pluripotency. A recent report shows that β-catenin achieves some of these effects by modulating the activity of Tcf3, and that this effect does not require its transcriptional activation domain. Here, we show that during self-renewal there is negligible transcriptional activity of β-catenin and that this is due to its tight association with membranes, where we find it in a complex with Oct4 and E-cadherin. Differentiation triggers a burst of Wnt/β-catenin transcriptional activity that coincides with the disassembly of the complex. Our results establish that β-catenin, but not its transcriptional activity, is central to pluripotency acting through a β-catenin/Oct4 complex.
authors: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors: Fernando
authors: F
authors: Faunes
authors: Penelope
authors: P
authors: Hayward
authors: Silvia Muñoz
authors: SM
authors: Descalzo
authors: Sujash S
authors: SS
authors: Chatterjee
authors: Tina
authors: T
authors: Balayo
authors: Jamie
authors: J
authors: Trott
authors: Andrew
authors: A
authors: Christoforou
authors: Anna
authors: A
authors: Ferrer-Vaquer
authors: Anna-Katerina
authors: AK
authors: Hadjantonakis
authors: Ramanuj
authors: R
authors: Dasgupta
authors: Alfonso Martinez
authors: AM
authors: Arias
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism* / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism* / Q000502:physiology
chemical_list: D046912:Multiprotein Complexes; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D051176:beta Catenin