kdm4aa knockout disturbs early embryonic development in Zebrafish via downregulating rbm46

Histone lysine-specific demethylase 4A (KDM4A) plays a critical role in the embryonic development of mammals such as mouse and goat, however its function in zebrafish (Danio rerio) embryogenesis remains poorly understood, due to the existence of two kdm4a paralogs (kdm4aa and kdm4ab) in zebrafish. The current study revealed that kdm4aa^-/- embryos exhibited dramatically increased mortality during gastrulation. RT-qPCR showed that RNA-binding motif protein 46 (rbm46) was downregulated after kdm4aa knockout. CUT&Tag-qPCR revealed that kdm4aa knockout significantly decreased H3K4me3, while increasing H3K9me3 and H3K36me3 at rbm46 promoter. kdm4aa^-/- embryos displayed elevated reactive oxygen species (ROS) and reduced adenosine triphosphate (ATP). And rbm46 mRNA injection alleviated ROS accumulation and increased ATP level, thereby rescuing the lethal phenotype in kdm4aa^-/- embryos. Our findings demonstrate that kdm4aa knockout disturbs zebrafish embryogenesis by suppressing rbm46 mRNA expression.