Publication on epigenetics during development


Zebrafish tissue integrity is compromised when the essential protein Ezh2 is absent

Bilge San and Naomi Chrispijn, PhD students in the research group headed by Leonie Kamminga, Dept. of Mol. Biology, theme Cancer development and immune defense published a research paper in Scientific Reports in which they describe the effects of loss of the protein Ezh2 on zebrafish tissue integrity.

One of the oldest questions in developmental biology is how multi-organ systems can be formed using the genomic material from one cell; the zygote. The phenomenon that explains this process is called epigenetics. Epigenetics is a high order of regulation on the genome, and it controls the activation and repression of different genes at different time points throughout embryogenesis and adulthood. Over time, tissue specific genes get activated to specify organs, and early embryonic genes get repressed. Gene repression occurs with the aid of proteins that tightly package the DNA into a folded structure, making the genes inaccessible for RNA transcription. The current research paper focuses on the protein Ezh2, which is such an epigenetic gene repressor. Ezh2¹s function in early development was studied using ezh2 mutant zebrafish as a model. It was found that embryos obtain ezh2 mRNA from their mother, and that the lack of ezh2 contribution from the mother influences the transfer of other maternal mRNAs to the zygote. In early stages during development, embryos that lack Ezh2 show major changes in their overall gene expression. However, morphological abnormalities arise later during development, causing lethality two days after fertilization. The most pronounced defect we observed was that cells dissociate from the developing heart. These detaching cells have an ambiguity in gene expression; they fail to shut down early developmental genes, and hence cannot maintain tissue integrity. San, Chrispijn et al. show that ezh2 mutants lose their tissue specific gene expression pattern, resulting in severe problems in the maintenance of tissue integrity.

Publication SREP: Normal formation of a vertebrate body plan and loss of tissue maintenance in the absence of ezh2, 2016


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