Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
mSphere. 2021 Jun 30;6(3):e0120820. doi: 10.1128/mSphere.01208-20. Epub 2021 May 28.
Rediscovered as a potential epigenetic mark, N-methyladenine DNA modification (6mA) was recently reported to be sensitive to environmental stressors in several multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. Here, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Single-molecule, real-time (SMRT) sequencing reveals that DNA 6mA levels in starved cells are significantly reduced, especially symmetric 6mA, compared to those in vegetatively growing cells. Despite a global 6mA reduction, the fraction of asymmetric 6mA with a high methylation level was increased, which might be the driving force for stronger nucleosome positioning in starved cells. Starvation affects expression of many metabolism-related genes, the expression level change of which is associated with the amount of 6mA change, thereby linking 6mA with global transcription and starvation adaptation. The reduction of symmetric 6mA and the increase of asymmetric 6mA coincide with the downregulation of AMT1 and upregulation of AMT2 and AMT5, which are supposedly the MT-A70 methyltransferases required for symmetric and asymmetric 6mA, respectively. These results demonstrated that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes. Increasing evidence indicated that 6mA could respond to environmental stressors in multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. In the present work, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Our results provide insights into how fine-tunes its 6mA level and composition upon starvation, suggesting that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes.
作为一种新发现的潜在表观遗传标记，N6-甲基腺嘌呤（6mA）DNA 修饰最近被报道在几种多细胞真核生物中对环境胁迫敏感。由于 6mA 在多细胞和单细胞生物中的分布和功能有很大差异，单细胞真核生物中的 6mA 是否以及如何对环境胁迫做出响应仍然难以捉摸。在这里，我们描述了单细胞真核模式生物嗜热四膜虫在饥饿状态下 6mA 的动态变化。单分子实时（SMRT）测序显示，与营养生长细胞相比，饥饿细胞中的 DNA 6mA 水平显著降低，尤其是对称 6mA。尽管 6mA 整体减少，但高甲基化水平的不对称 6mA 比例增加，这可能是饥饿细胞中核小体定位更强的驱动力。饥饿会影响许多与代谢相关基因的表达，这些基因表达水平的变化与 6mA 变化量相关，从而将 6mA 与全局转录和饥饿适应联系起来。对称 6mA 的减少和不对称 6mA 的增加与 AMT1 的下调和 AMT2 和 AMT5 的上调相吻合，这两种酶可能分别是对称和不对称 6mA 所需的 MT-A70 甲基转移酶。这些结果表明，受调控的 6mA 对环境信号的响应在真核生物中是进化保守的。越来越多的证据表明，6mA 可以响应多细胞真核生物中的环境胁迫。由于 6mA 在多细胞和单细胞生物中的分布和功能有很大差异，单细胞真核生物中的 6mA 是否以及如何对环境胁迫做出响应仍然难以捉摸。在本工作中，我们描述了单细胞模型生物嗜热四膜虫在饥饿状态下 6mA 的动态变化。我们的研究结果为了解细胞如何在饥饿时精细调节 6mA 水平和组成提供了线索，表明受调控的 6mA 对环境信号的响应在真核生物中是进化保守的。
