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The chromodomain helicase Chd4 is required for Polycomb‐mediated inhibition of astroglial differentiation
Author(s) -
Sparmann Anke,
Xie Yunli,
Verhoeven Els,
Vermeulen Michiel,
Lancini Cesare,
Gargiulo Gaetano,
Hulsman Danielle,
Mann Matthias,
Knoblich Juergen A,
van Lohuizen Maarten
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.93
Subject(s) - chromodomain , biology , helicase , polycomb group proteins , microbiology and biotechnology , genetics , gene , gene expression , repressor , rna
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.