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

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,...

Full description

Saved in:
Bibliographic Details
Published inNature communications Vol. 6; no. 1; p. 6749
Main Authors Abboud, Nesrine, Morris, Thomas Moore, Hiriart, Emilye, Yang, Henry, Bezerra, Hudson, Gualazzi, Maria-Giovanna, Stefanovic, Sonia, Guénantin, Anne-Claire, Evans, Sylvia M., Pucéat, Michel
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 08.04.2015
Nature Publishing Group
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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 Sox s loci. Thus, OCT4/SALL4-driven cohesin- and polycombs-mediated changes in higher-order chromatin structure mediate instruction of early cell fate in embryonic cells. Higher order chromatin structures affect gene transcription, but how they determine cell fate is unclear. Here, the authors show that OCT4 and SALL4 alter the higher-order chromatin structure and mediate cell fate switching in embryonic cells by targeting cohesin and polycomb complexes, respectively.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally to this work
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms7749