<i>kdm4aa</i> knockout disturbs early embryonic development in Zebrafish via downregulating <i>rbm46</i>

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 (<i>Danio rerio</i>) embryogenesis remains poorly understood, due to the existence of two <i>kdm4a</i> paralogs (<i>kdm4aa</i> and <i>kdm4ab</i>) in zebrafish. The current study revealed that <i>kdm4aa</i>^-/- embryos exhibited dramatically increased mortality during gastrulation. RT-qPCR showed that RNA-binding motif protein 46 (<i>rbm46</i>) was downregulated after <i>kdm4aa</i> knockout. CUT&Tag-qPCR revealed that <i>kdm4aa</i> knockout significantly decreased H3K4me3, while increasing H3K9me3 and H3K36me3 at <i>rbm46</i> promoter. <i>kdm4aa</i>^-/- embryos displayed elevated reactive oxygen species (ROS) and reduced adenosine triphosphate (ATP). And <i>rbm46</i> mRNA injection alleviated ROS accumulation and increased ATP level, thereby rescuing the lethal phenotype in <i>kdm4aa</i>^-/- embryos. Our findings demonstrate that <i>kdm4aa</i> knockout disturbs zebrafish embryogenesis by suppressing <i>rbm46</i> mRNA expression.