The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation
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The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation. / Sparmann, Anke; Xie, Yunli; Verhoeven, Els; Vermeulen, Michiel; Lancini, Cesare; Gargiulo, Gaetano; Hulsman, Danielle; Mann, Matthias; Knoblich, Juergen A; van Lohuizen, Maarten.
In: E M B O Journal, Vol. 32, No. 11, 29.05.2013, p. 1598-612.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation
AU - Sparmann, Anke
AU - Xie, Yunli
AU - Verhoeven, Els
AU - Vermeulen, Michiel
AU - Lancini, Cesare
AU - Gargiulo, Gaetano
AU - Hulsman, Danielle
AU - Mann, Matthias
AU - Knoblich, Juergen A
AU - van Lohuizen, Maarten
PY - 2013/5/29
Y1 - 2013/5/29
N2 - 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.
AB - 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.
KW - Animals
KW - Astrocytes
KW - Cell Differentiation
KW - Cell Line
KW - Chromatin Immunoprecipitation
KW - DNA Helicases
KW - Embryo, Mammalian
KW - Female
KW - Gene Expression Regulation, Developmental
KW - Histones
KW - Mice
KW - Mice, Inbred C57BL
KW - Nerve Tissue Proteins
KW - Neural Stem Cells
KW - Nuclear Proteins
KW - Polycomb Repressive Complex 2
KW - Polycomb-Group Proteins
KW - Pregnancy
KW - Promoter Regions, Genetic
U2 - 10.1038/emboj.2013.93
DO - 10.1038/emboj.2013.93
M3 - Journal article
C2 - 23624931
VL - 32
SP - 1598
EP - 1612
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 11
ER -
ID: 88584618