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The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation

Item Type:Article
Title:The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation
Creators Name:Sparmann, A. and Xie, Y. and Verhoeven, E. and Vermeulen, M. and Lancini, C. and Gargiulo, G. and Hulsman, D. and Mann, M. and Knoblich, J.A. and van Lohuizen, M.
Abstract:Polycomb group (PcG) proteins form transcriptional repressor complexes with well-established functions during cell-fate determination. Yet, the mechanisms underlying their regulation remain poorly understood. Here, we extend the role of Polycomb complexes in the temporal control of neural progenitor cell (NPC) commitment by demonstrating that the PcG protein Ezh2 is necessary to prevent the premature onset of gliogenesis. In addition, we identify the chromodomain helicase DNA-binding protein 4 (Chd4) as a critical interaction partner of Ezh2 required specifically for PcG-mediated suppression of the key astrogenic marker gene GFAP. Accordingly, in vivo depletion of Chd4 in the developing neocortex promotes astrogenesis. Collectively, these results demonstrate that PcG proteins operate in a highly dynamic, developmental stage-dependent fashion during neural differentiation and suggest that target gene-specific mechanisms regulate Polycomb function during sequential cell-fate decisions.
Keywords:Astrogenesis, Chd4, Differentiation, Neural Stem Cells, Polycomb, Animals, Mice
Source:EMBO Journal
ISSN:0261-4189
Publisher:Wiley-Blackwell (U.S.A.)
Volume:32
Number:11
Page Range:1598-1612
Date:29 May 2013
Official Publication:https://doi.org/10.1038/emboj.2013.93
PubMed:View item in PubMed

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