title: Sall4 controls differentiation of pluripotent cells independently of the Nucleosome Remodelling and Deacetylation (NuRD) complex.
abstract: Sall4 is an essential transcription factor for early mammalian development and is frequently overexpressed in cancer. Although it is reported to play an important role in embryonic stem cell (ESC) self-renewal, whether it is an essential pluripotency factor has been disputed. Here, we show that Sall4 is dispensable for mouse ESC pluripotency. Sall4 is an enhancer-binding protein that prevents precocious activation of the neural gene expression programme in ESCs but is not required for maintenance of the pluripotency gene regulatory network. Although a proportion of Sall4 protein physically associates with the Nucleosome Remodelling and Deacetylase (NuRD) complex, Sall4 neither recruits NuRD to chromatin nor influences transcription via NuRD; rather, free Sall4 protein regulates transcription independently of NuRD. We propose a model whereby enhancer binding by Sall4 and other pluripotency-associated transcription factors is responsible for maintaining the balance between transcriptional programmes in pluripotent cells.
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK Department of Biochemistry, University of Cambridge, Cambridge CB2 1QR, UK.
authors.forename: Anzy
authors.initials: A
authors.lastname: Miller
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK.
authors.forename: Meryem
authors.initials: M
authors.lastname: Ralser
authors.affiliation: Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, 6525 GA Nijmegen, The Netherlands.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kloet
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
authors.forename: Remco
authors.initials: R
authors.lastname: Loos
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.affiliation: Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, 6525 GA Nijmegen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.affiliation: Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK Department of Biochemistry, University of Cambridge, Cambridge CB2 1QR, UK brian.hendrich@cscr.cam.ac.uk.
authors.forename: Brian
authors.identifier: 0000-0002-0231-3073
authors.initials: B
authors.lastname: Hendrich
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D013058:Mass Spectrometry; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009707:Nucleosomes; C509167:Sall4 protein, mouse; D014157:Transcription Factors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: Co-repressor; ES cells; Enhancer; NuRD; Sall4; Transcription factor