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Open Access Highly Accessed Research article

Sox2 acts as a transcriptional repressor in neural stem cells

Yu-Ru Liu1, Zulfiqar A Laghari2, Carolina A Novoa3, Jaime Hughes1, Jamie RM Webster1, Paul E Goodwin1, Sally P Wheatley1 and Paul J Scotting1*

Author Affiliations

1 Centre for Genetics and Genomics, School of Life Sciences, Queen’s Medical Centre, Nottingham NG7 2UH, England

2 Department of Physiology, University of Sindh, Jamshoro, Pakistan

3 BCCRC, 675 West 10th Avenue, Vancouver, BC, Canada

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BMC Neuroscience 2014, 15:95  doi:10.1186/1471-2202-15-95

Published: 8 August 2014

Abstract

Background

The transcription factor, Sox2, is central to the behaviour of neural stem cells. It is also one of the key embryonic stem cell factors that, when overexpressed can convert somatic cells into induced pluripotent cells. Although generally studied as a transcriptional activator, recent evidence suggests that it might also repress gene expression.

Results

We show that in neural stem cells Sox2 represses as many genes as it activates. We found that Sox2 interacts directly with members of the groucho family of corepressors and that repression of several target genes required this interaction. Strikingly, where many of the genes activated by Sox2 encode transcriptional regulators, no such genes were repressed. Finally, we found that a mutant form of Sox2 that was unable to bind groucho was no longer able to inhibit differentiation of neural stem cells to the same extent as the wild type protein.

Conclusions

These data reveal a major new mechanism of action for this key transcription factor. In the context of our understanding of endogenous stem cells, this highlights the need to determine how such a central regulator can distinguish which genes to activate and which to repress.

Keywords:
Sox2; Groucho; Grg; Repressor; Neural stem cells