During early embryogenesis, the embryo is absent of gene transcription and instead regulated by maternal mRNA and proteins. Therefore, maternal factors drive early embryogenesis, and it is very meaningful to identity the maternal transcripts that are vital for early embryogenesis. Histone lysine methylation has been proved to be an important post-translational modification involved in transcriptional regulation during early embryogenesis. However, the studies about histone arginine methylation are less. It is known that H3R2me2a, an important repressive marker, is methylated primarily by Prmt6. Prmt6 has been reported to regulate many biological processes, including signal transduction, RNA procession, and transcription. Prmt6 is upregulated in various cancer types, and facilitates proliferation and blocks senescence. The roles of Prmt6 in early embryogenesis remain unknown. 

Under the guidance of Prof. LI Yiping, ZHAO et al designed to explore the role of Prmt6 and H3R2me2a during zebrafish embryogenesis. The first author of this study is a graduate student ZHAO Xinxi from the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences. The results from RT-PCR and whole mount in situ hybridization demonstrated that prmt6 is a maternally derived transcript, suggesting it has a role during early zebrafish development. Two prmt6-specific morpholino-oligos (MOs) were designed, application of which led to early epiboly defects, and significantly reduced the level of H3R2me2a marks. Rescue experiments indicated that the phenotype of prmt6 morphants is specific and depends on the enzymatic activity of Prmt6. A gene microarray was performed in control embryos and in the prmt6 morphants. 

Interestingly, the stress sensor gene gadd45αa was the top upregulated gene in the list. Rescue experiments proved that the upregulation of gadd45αa is responsible for the prmt6 morphants. The upregulation of gadd45αa was linked to the activation of the p38/JNK pathway and apoptosis. Moreover, the results of ChIP-qPCR and Luciferase Reporter Assay indicated that gadd45αa is a repressive target of Prmt6.  

Taken together, these results suggest that maternal Prmt6 is essential to early zebrafish development by directly repressing gadd45αa. 

This study entitled “Protein Arginine Methyltransferase 6 (Prmt6) Is Essential for Early Zebrafish Development through the Direct Suppression of gadd45αa Stress Sensor Gene” has been published in Journal of Biological Chemistry on January 1, 2016. 

This work was supported by the grants from the Ministry of Science and Technology of China, and the Shanghai Science and Technology Commission. The main experiments have been carried out on the Core Facility for Zebrafish, the Core Facility for Cell Biology, and the Core Facility for Molecular Biology at SIBCB.