title: A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.
abstract: Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One of the first embryonic cell fate decisions (that is, mesendoderm determination) is driven by the POU factor OCT4, acting in concert with the high-mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling mechanism and enhancer function that mediate cell fate switching. OCT4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out cohesin and switches the Sox-17 enhancer from a locked (within an inter-chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active (within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4 concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4-driven cohesin- and polycombs-mediated changes in higher-order chromatin structure mediate instruction of early cell fate in embryonic cells.
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.
authors: Nesrine
authors: N
authors: Abboud
authors: INSERM UMR 910, GMGF, Aix-Marseille University, 13885 Marseille, France.
authors: Thomas Moore-
authors: TM
authors: Morris
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.|INSERM UMR 910, GMGF, Aix-Marseille University, 13885 Marseille, France.
authors: Emilye
authors: E
authors: Hiriart
authors: Cancer Science Institute, National University of Singapore, Singapore 138672, Singapore.
authors: Henry
authors: H
authors: Yang
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.
authors: Hudson
authors: H
authors: Bezerra
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.
authors: Maria-Giovanna
authors: MG
authors: Gualazzi
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.|INSERM UMR 910, GMGF, Aix-Marseille University, 13885 Marseille, France.
authors: Sonia
authors: S
authors: Stefanovic
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.
authors: Anne-Claire
authors: AC
authors: Guénantin
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Medecine and Department of Pharmacology, UCSD, La Jolla, California 92093, California, USA.
authors: Sylvia M
authors: SM
authors: Evans
authors: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France.|INSERM UMR 910, GMGF, Aix-Marseille University, 13885 Marseille, France.
authors: Michel
authors: M
authors: Pucéat
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D000066449:Human Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055747:SOX Transcription Factors / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000097722:Cohesins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D024002:HMGB Proteins; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D055747:SOX Transcription Factors; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors; D014157:Transcription Factors; D000097722:Cohesins; C069077:BMI1 protein, human; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C101538:Mesp1 protein, mouse; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; C472575:SALL4 protein, human; C430461:SUZ12 protein, human; C509167:Sall4 protein, mouse; C511606:Sox17 protein, mouse; C527783:Sox2 protein, mouse