Hayashi, Y., Hino, S., Sato, T., Kashio, S., Otsubo, K., Saito, K., Sato, B., Kawano, N., Saito, D., Miura, M., Suyama, M., Nakao, M., Kobayashi, S. (2025). Repressive S-adenosylmethionine biosynthesis status inhibits transcription of HeT-A retrotransposon in the germline of Drosophila.  J. Biochem., Tokyo 178(4): 217--228.

FBrf0263486

Research paper

S-adenosylmethionine (SAM) is the major cellular methyl donor and regulates gene expression through epigenetic and other methylation-related processes. While SAM biosynthesis influences a variety of biological phenomena including ageing and disease, its cell type-specific regulation and functional implications remain poorly understood. In this study, we report that the Drosophila germline exhibits a uniquely repressive SAM biosynthesis status during gametogenesis, as indicated by low expression of SAM synthetase (Sam-S), a key enzyme for SAM production. Experimentally enhancing SAM biosynthesis in the germline led to increased expression of retrotransposons, with HeT-A, a telomere-specific element, showing the most pronounced response. We also observed increased promoter activity of HeT-A under high SAM conditions, along with accumulation of N6-methyladenine (6 mA), the major form of DNA methylation in the Drosophila genome. Although a direct causal link between 6 mA levels and transcription was not broadly observed across other retrotransposons or genes, these results raise the possibility that SAM levels modulate HeT-A expression at least in part through DNA methylation. Our findings highlight a previously underexplored metabolic feature of the Drosophila germline and suggest that SAM availability contributes to the regulation of retrotransposon activity in a lineage-specific manner.