期刊
EPIGENOMES
卷 2, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/epigenomes2040019
关键词
zebrafish; development; ENU mutagenesis; Polycomb repressive complex 2; gene expression; transcriptomics; epigenetics; Ezh2
资金
- Innovative Research scheme of the Netherlands Organisation for Scientic research [NWO-Veni 916.96.021, NWO-Vidi 864.12.009, NWO-Vidi 864.09.005]
- Radboud University Nijmegen Medical Centre tenure track fellowship
Many regulatory pathways are conserved in the zebrafish intestine compared to mammals, rendering it a strong model to study intestinal development. However, the (epi)genetic regulation of zebrafish intestinal development remains largely uncharacterized. We performed RNA-sequencing and chromatin immunoprecipitation (ChIP)-sequencing for activating (H3K4me3) and repressive (H3K27me3) chromatin marks on isolated intestines at 5, 7, and 9 days post-fertilization (dpf), during which zebrafish transit from yolk dependence to external feeding. RNA-sequencing showed the enrichment of metabolic maintenance genes at all time points and a significant increase in lipid metabolism between 5 and 9 dpf. A strong correlation was observed between gene expression and presence of chromatin marks on gene promoters; H3K4me3-marked genes were expressed higher than H3K27m3-marked genes. Next, we studied a key epigenetic player, Enhancer of zeste homolog 2 (Ezh2). Ezh2 places the repressive H3K27me3 mark on the genome and is highly conserved in vertebrates. We used the nonsense mutant allele ezh2(hu5670) to study the effect of ezh2 loss on intestinal development. These mutants survived gastrulation and died around 11 dpf, showing severe morphological defects in the intestine and liver, accompanied by decreased intestinal (fabp2) and hepatic (fabp10a) marker expressions. Our results suggest that Ezh2 is essential for proper intestinal tissue maintenance and overall survival.
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