title: The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation.
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.
authors.affiliation: Division of Molecular Genetics, Center for Biomedical Genetics and Netherlands Proteomics Center, The Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Sparmann
authors.forename: Yunli
authors.initials: Y
authors.lastname: Xie
authors.forename: Els
authors.initials: E
authors.lastname: Verhoeven
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Cesare
authors.initials: C
authors.lastname: Lancini
authors.forename: Gaetano
authors.initials: G
authors.lastname: Gargiulo
authors.forename: Danielle
authors.initials: D
authors.lastname: Hulsman
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
authors.forename: Maarten
authors.initials: M
authors.lastname: van Lohuizen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic
chemical_list: D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; C528900:glial fibrillary astrocytic protein, mouse; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases