Document Detail


Sox2 Acts in a Dose-Dependent Fashion to Regulate Proliferation of Cortical Progenitors.
MedLine Citation:
PMID:  25482558     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Organ formation and maintenance depends on slowly self-renewing stem cells that supply an intermediate population of rapidly dividing progenitors, but how this proliferative hierarchy is regulated is unknown. By performing genome-wide single-cell and functional analyses in the cortex, we demonstrate that reduced Sox2 expression is a key regulatory signature of the transition between stem cells and rapidly dividing progenitors. In stem cells, Sox2 is expressed at high levels, which enables its repression of proproliferative genes, of which Cyclin D1 is the most potent target. Sox2 confers this function through binding to low-affinity motifs, which facilitate the recruitment of Gro/Tle corepressors in synergy with Tcf/Lef proteins. Upon differentiation, proneural factors reduce Sox2 expression, which derepresses Cyclin D1 and promotes proliferation. Our results show how concentration-dependent Sox2 occupancy of DNA motifs of varying affinities translates into recruitment of repressive complexes, which regulate the proliferative dynamics of neural stem and progenitor cells.
Authors:
Daniel W Hagey; Jonas Muhr
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-3
Journal Detail:
Title:  Cell reports     Volume:  -     ISSN:  2211-1247     ISO Abbreviation:  Cell Rep     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-8     Completed Date:  -     Revised Date:  2014-12-9    
Medline Journal Info:
Nlm Unique ID:  101573691     Medline TA:  Cell Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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