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Sci Rep. 2016 May 5;6:24658. doi: 10.1038/srep24658.

Normal formation of a vertebrate body plan and loss of tissue maintenance in the absence of ezh2.

Author information

1
Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
2
Radboud University, Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
3
Hubrecht Institute, University Medical Centre Utrecht, Utrecht, The Netherlands.
4
Institute of Molecular Biology, Mainz, Germany.
5
Radboud University, Faculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
6
Medical Physiology, University Medical Centre Utrecht, Utrecht, The Netherlands.

Abstract

Polycomb group (PcG) proteins are transcriptional repressors of numerous genes, many of which regulate cell cycle progression or developmental processes. We used zebrafish to study Enhancer of zeste homolog 2 (Ezh2), the PcG protein responsible for placing the transcriptional repressive H3K27me3 mark. We identified a nonsense mutant of ezh2 and generated maternal zygotic (MZ) ezh2 mutant embryos. In contrast to knockout mice for PcG proteins, MZezh2 mutant embryos gastrulate seemingly normal, but die around 2 days post fertilization displaying pleiotropic phenotypes. Expression analyses indicated that genes important for early development are not turned off properly, revealing a regulatory role for Ezh2 during zygotic gene expression. In addition, we suggest that Ezh2 regulates maternal mRNA loading of zygotes. Analyses of tissues arising later in development, such as heart, liver, and pancreas, indicated that Ezh2 is required for maintenance of differentiated cell fates. Our data imply that the primary role of Ezh2 is to maintain tissues after tissue specification. Furthermore, our work indicates that Ezh2 is essential to sustain tissue integrity and to set up proper maternal mRNA contribution, and presents a novel and powerful tool to study how PcG proteins contribute to early vertebrate development.

PMID:
27145952
PMCID:
PMC4857124
DOI:
10.1038/srep24658
[Indexed for MEDLINE]
Free PMC Article

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