title: Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency.
abstract: The transcription factors OCT4 and SOX2 are required for generating induced pluripotent stem cells (iPSCs) and for maintaining embryonic stem cells (ESCs). OCT4 and SOX2 associate and bind to DNA in different configurations depending on the arrangement of their individual DNA binding elements. Here we have investigated the role of the different OCT4-SOX2-DNA assemblies in regulating and inducing pluripotency. To this end, we have generated SOX2 mutants that interfere with specific OCT4-SOX2 heterodimer configurations and assessed their ability to generate iPSCs and to rescue ESC self-renewal. Our results demonstrate that the OCT4-SOX2 configuration that dimerizes on a Hoxb1-like composite, a canonical element with juxtaposed individual binding sites, plays a more critical role in the induction and maintenance of pluripotency than any other OCT4-SOX2 configuration. Overall, the results of this study provide new insight into the protein interactions required to establish a de novo pluripotent network and to maintain a true pluripotent cell fate.
authors: Heinrich Heine University, Faculty of Medicine, Moorenstraße 5, 40225 Düsseldorf, Germany.|Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgentstraße, 20, Münster 48149, Germany.
authors: Natalia
authors: N
authors: Tapia
authors: Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgentstraße, 20, Münster 48149, Germany.
authors: Caitlin
authors: C
authors: MacCarthy
authors: Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgentstraße, 20, Münster 48149, Germany.
authors: Daniel
authors: D
authors: Esch
authors: Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgentstraße, 20, Münster 48149, Germany.
authors: Adele
authors: A
authors: Gabriele Marthaler
authors: Heinrich Heine University, Faculty of Medicine, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors: Ulf
authors: U
authors: Tiemann
authors: Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, Doctor Begiristain s/n, 20014 San Sebastián, Spain.|IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, 48011 Bilbao, Spain.
authors: Marcos J
authors: MJ
authors: Araúzo-Bravo
authors: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.|Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Ralf
authors: R
authors: Jauch
authors: Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgentstraße, 20, Münster 48149, Germany.
authors: Vlad
authors: V
authors: Cojocaru
authors: Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgentstraße, 20, Münster 48149, Germany.
authors: Hans R
authors: HR
authors: Schöler
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D000066449:Human Embryonic Stem Cells; D006801:Humans; D008822:Mice, Transgenic; D008958:Models, Molecular; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D055503:Protein Multimerization; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
chemical_list: D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors