Duan Lili, Li Haicheng, Ju Aili, Zhang Zhe, Niu Junhua, Zhang Yumiao, Diao Jinghan, Liu Yongqiang, Song Ni, Ma Honggang, Kataoka Kensuke, Gao Shan, Wang Yuanyuan
MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.
Laboratory for Marine Biology and Biotechnology, Laoshan Laboratory, Qingdao 266237, China.
Nucleic Acids Res. 2025 Jan 24;53(3). doi: 10.1093/nar/gkaf022.
DNA N6-methyladenine (6mA) is a potential epigenetic mark involved in gene transcription in eukaryotes, yet the regulatory mechanism governing its methyltransferase (MTase) activity remains obscure. Here, we exploited the 6mA MTase AMT1 to elucidate its auto-regulation in the unicellular eukaryote Tetrahymena thermophila. The detailed endogenous localization of AMT1 in vegetative and sexual stages revealed a correlation between the 6mA reestablishment in the new MAC and the occurrence of zygotically expressed AMT1. Catalytically inactive AMT1 reduced 6mA level on the AMT1 gene and its expression, suggesting that AMT1 modulated its own transcription via 6mA. Furthermore, AMT1-dependent 6mA regulated the transcription of its target genes, thereby affecting cell fitness. Our findings unveil a positive feedback loop of transcriptional activation on the AMT1 gene and highlight the crucial role of AMT1-dependent 6mA in gene transcription.
DNA N6-甲基腺嘌呤（6mA）是一种潜在的表观遗传标记，参与真核生物中的基因转录，但其甲基转移酶（MTase）活性的调控机制仍不清楚。在这里，我们利用6mA甲基转移酶AMT1来阐明其在单细胞真核生物嗜热四膜虫中的自我调节。AMT1在营养期和有性期的详细内源性定位揭示了新MAC中6mA重新建立与合子表达的AMT1出现之间的相关性。催化无活性的AMT1降低了AMT1基因上的6mA水平及其表达，表明AMT1通过6mA调节自身转录。此外，AMT1依赖性6mA调节其靶基因的转录，从而影响细胞适应性。我们的发现揭示了AMT1基因转录激活的正反馈回路，并突出了AMT1依赖性6mA在基因转录中的关键作用。
