Knockout of kdm4aa Inhibits Early Embryonic Development in Zebrafish via Downregulating cyp26a1

There are two copies of the kdm4a gene in zebrafish (Danio rerio), namely kdm4aa and kdm4ab. Our previous study showed that knockout of kdm4aa severely disturbs early embryonic development in zebrafish, here we investigated the underlying mechanism.

Knockout of kdm4aa in zebrafish resulted in a clearly developmental delay and embryonic lethality, accompanied by increased apoptosis. RT-qPCR and CUT&Tag-qPCR showed kdm4aa knockout downregulated Cytochrome P450 26a1 (cyp26a1), probably through elevated enrichment of H3K9me3 and reduced enrichment of H3K4me3 at promoter region of cyp26a1. Further experiments confirmed that cyp26a1 mRNA partially alleviates stress-induced apoptosis in both WT and kdm4aa knockout embryos, consistent with its known anti-apoptotic function.