{"title":"Repressive S-adenosylmethionine biosynthesis status inhibits transcription of HeT-A retrotransposon in the germline of Drosophila.","authors":"Yoshiki Hayashi, Shinjiro Hino, Tetsuya Sato, Soshiro Kashio, Kiito Otsubo, Kuniaki Saito, Ban Sato, Natsuko Kawano, Daisuke Saito, Masayuki Miura, Mikita Suyama, Mitsuyoshi Nakao, Satoru Kobayashi","doi":"10.1093/jb/mvaf041","DOIUrl":null,"url":null,"abstract":"<p><p>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 aging 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 (6mA), the major form of DNA methylation in the Drosophila genome. Although a direct causal link between 6mA 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.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/jb/mvaf041","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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 aging 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 (6mA), the major form of DNA methylation in the Drosophila genome. Although a direct causal link between 6mA 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.
s -腺苷蛋氨酸(SAM)是主要的细胞甲基供体,通过表观遗传和其他甲基化相关过程调节基因表达。虽然SAM生物合成影响包括衰老和疾病在内的多种生物现象,但其细胞类型特异性调节和功能含义仍然知之甚少。在这项研究中,我们报道了果蝇种系在配子体发生过程中表现出一种独特的抑制SAM生物合成状态,这表明SAM合成酶(SAM - s)的低表达,SAM合成酶是SAM生产的关键酶。在实验中,增强种系SAM生物合成导致反转录转座子的表达增加,其中端粒特异性元件HeT-A表现出最明显的反应。我们还观察到,在高SAM条件下,HeT-A启动子活性增加,同时n6 -甲基腺嘌呤(6mA)积累,这是果蝇基因组中DNA甲基化的主要形式。尽管在其他反转录转座子或基因中没有广泛观察到6mA水平与转录之间的直接因果关系,但这些结果提出了SAM水平至少部分通过DNA甲基化调节HeT-A表达的可能性。我们的研究结果强调了以前未被充分探索的果蝇种系代谢特征,并表明SAM的可用性有助于以谱系特异性的方式调节反转录转座子活性。
期刊介绍:
The Journal of Biochemistry founded in 1922 publishes the results of original research in the fields of Biochemistry, Molecular Biology, Cell, and Biotechnology written in English in the form of Regular Papers or Rapid Communications. A Rapid Communication is not a preliminary note, but it is, though brief, a complete and final publication. The materials described in Rapid Communications should not be included in a later paper. The Journal also publishes short reviews (JB Review) and papers solicited by the Editorial Board.