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

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...

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Vydáno v:	The EMBO journal Ročník 32; číslo 11; s. 1598 - 1612
Hlavní autoři:	Sparmann, Anke, Xie, Yunli, Verhoeven, Els, Vermeulen, Michiel, Lancini, Cesare, Gargiulo, Gaetano, Hulsman, Danielle, Mann, Matthias, Knoblich, Juergen A, van Lohuizen, Maarten
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Chichester, UK John Wiley & Sons, Ltd 29.05.2013 Nature Publishing Group UK Springer Nature B.V Nature Publishing Group
Témata:	Animals Astrocytes - cytology Astrocytes - metabolism astrogenesis Cell Differentiation Cell Line Cells Chd4 Chromatin Immunoprecipitation Deoxyribonucleic acid Developmental stages differentiation DNA DNA Helicases - genetics DNA Helicases - metabolism EMBO09 EMBO27 Embryo, Mammalian Enhancer of Zeste Homolog 2 Protein Female Gene Expression Regulation, Developmental Glial Fibrillary Acidic Protein Histones - chemistry Histones - metabolism Mice Mice, Inbred C57BL Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neural networks neural stem cells Neural Stem Cells - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism polycomb Polycomb Repressive Complex 2 - genetics Polycomb Repressive Complex 2 - metabolism Polycomb-Group Proteins - genetics Polycomb-Group Proteins - metabolism Pregnancy Promoter Regions, Genetic Proteins Signal transduction astrogenesis differentiation Chd4 neural stem cells polycomb
ISSN:	0261-4189, 1460-2075, 1460-2075
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Shrnutí:	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. The Polycomb Group (PcG) transcriptional repressor complex interacts with Chd4 to suppress the astrogenic marker GFAP, thereby preventing premature gliogensis during neocortical development.
Bibliografie:	Supplementary InformationSupplementary Figure S1Supplementary Figure S2Supplementary Figure S3Supplementary Figure S4Supplementary Figure S5Supplementary Figure S6Supplementary Figure S7Supplementary Table 1Review Process FileSource Data for Figure 1Source Data for Figure 2Source Data for Figure 3Source Data for Figure 4Source Data for Figure 7c ark:/67375/WNG-98D3JPQ3-T istex:C2AC72F34C400CB22A4090E44A2AABDFE61B83F1 ArticleID:EMBJ201393 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Present address: Department of Molecular Cancer Research, University Medical Centre Utrecht, 3584CG Utrecht, The Netherlands These authors contributed equally to this work
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.1038/emboj.2013.93