DNA methylation mediates gonadal development via regulating the expression levels of cyp19a1a in loach Misgurnus anguillicaudatus

DNA methylation-mediated transcriptional regulation has been considered to significantly impact some ste-roidogenic enzyme genes expression. To uncover the roles of DNA methylation on the regulation of aromatase gene expression during gametogenesis in Misgurnus anguillicaudatus, the expression profiles and cellular locali-zation of cyp19a1a and cyp19a1b were analyzed, and the landscape of DNA methylation dynamics was inves-tigated. We found that cyp19a1a was predominantly expressed in granulosa cells of oocytes, while cyp19a1b expression was enriched in radial glial cells of the forebrain. In ovary, cyp19a1a was highly expressed until the vitellogenesis stage. The average methylation levels, especially for two CpG sites within the cAMP response element, were negatively correlated with cyp19a1a expression levels, indicating that methylation could regulate cyp19a1a transcriptional activity by modulating the binding efficiency of cAMP to its response elements. Compared with in ovary, cyp19a1a showed lower expression in testis but was hypermethylated. Cyp19a1b in female brain weakly expressed before the vitellogenesis stage, but significantly elevated at the maturation stage. In both sexes, it maintained high methylation levels in brain despite the obvious fluctuation of the cyp19a1b expression. This study revealed that DNA methylation plays a key role in establishing cyp19a1a spatiotemporal expression patterns and thus mediates gonadal development in teleosts.

Automated summary

DNA methylation plays a crucial role in regulating the expression patterns of aromatase genes cyp19a1a and cyp19a1b during gametogenesis in Misgurnus anguillicaudatus. Methylation negatively regulates the expression of cyp19a1a in the ovaries, while cyp19a1b expression fluctuates in the brain but maintains high methylation levels. This study highlights the importance of DNA methylation in mediating gonadal development in teleosts.