title: Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells.
abstract: We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state.
authors.affiliation: Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
authors.forename: Maciej
authors.initials: M
authors.lastname: Paszkowski-Rogacz
authors.affiliation: Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Winzi
authors.affiliation: Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
authors.forename: Debojyoti
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Theis
authors.affiliation: Genomics, Biotechnology Center, TU Dresden, 01307 Dresden, Germany.
authors.forename: Sukhdeep
authors.initials: S
authors.lastname: Singh
authors.affiliation: Genomics, Biotechnology Center, TU Dresden, 01307 Dresden, Germany.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciotta
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.affiliation: Department of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Wai Kit
authors.initials: WK
authors.lastname: Chu
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Chunaram
authors.initials: C
authors.lastname: Choudhary
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Genomics, Biotechnology Center, TU Dresden, 01307 Dresden, Germany.
authors.forename: A Francis
authors.initials: AF
authors.lastname: Stewart
authors.affiliation: Department of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Nevan
authors.initials: N
authors.lastname: Krogan
authors.affiliation: Medical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address: frank.buchholz@tu-dresden.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Buchholz