A cohesin–OCT4 complex mediates Sox enhancers to prime an early embryonic lineage

Nesrine Abboud, Thomas Moore- Morris, Emilye Hiriart, Henry Yang, Hudson Bezerra, Maria-Giovanna Gualazzi, Sonia Stefanovic, Anne-Claire Guénantin, Sylvia M. Evans and Michel Pucéat ()
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Nesrine Abboud: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France
Thomas Moore- Morris: INSERM UMR 910, GMGF, Aix-Marseille University
Emilye Hiriart: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France
Henry Yang: Cancer Science Institute, National University of Singapore
Hudson Bezerra: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France
Maria-Giovanna Gualazzi: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France
Sonia Stefanovic: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France
Anne-Claire Guénantin: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France
Sylvia M. Evans: Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD
Michel Pucéat: INSERM UMR 633, Genopole Evry, University Paris Descartes, 91000 Evry, Paris, France

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7749

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