title: Sox2 acts as a transcriptional repressor in neural stem cells.
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.
authors.forename: Yu-Ru
authors.initials: YR
authors.lastname: Liu
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Laghari
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Novoa
authors.forename: Jaime
authors.initials: J
authors.lastname: Hughes
authors.forename: Jamie R M
authors.initials: JR
authors.lastname: Webster
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goodwin
authors.forename: Sally P
authors.initials: SP
authors.lastname: Wheatley
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queen's Medical Centre, Nottingham NG7 2UH, England. paul.scotting@nottingham.ac.uk.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Scotting
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D009154:Mutation; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection
chemical_list: D056970:Co-Repressor Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse
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