DNA methylation on N6-adenine in lepidopteran Bombyx mori
DNA methylation on N6-adenine in lepidopteran Bombyx mori
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鳞翅目家蚕 N6-腺嘌呤 DNA 甲基化
DOI：
10.1016/j.bbagrm.2018.07.013
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发表时间：
2018-09-01
影响因子：
4.7
通讯作者：
Zhao, Ping
中科院分区：
文献类型：
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作者：
Wang, Xiaoyan;Li, Zhiqing;Zhao, Ping
DNA甲基化发生在腺嘌呤的第六位(N6-甲基腺嘌呤，6 mA)，已成为真核生物中一种新的表观遗传标记，在调控基因转录、DNA复制和修复、转座活性等方面发挥着重要作用。在这里，我们发现在鳞翅目模式昆虫家蚕中存在DNA 6 mA甲基化，并鉴定了6 mA甲基转移酶METTL4和6 mA去甲基酶NMAD，它们调节家蚕胚胎发育和培养细胞中6 mA甲基化水平。重要的是，METTL4和NMAD的RNAi敲除不仅导致细胞周期停滞在G1期，而且还导致中期染色体比对的缺陷。我们进一步证明6 mA甲基化通过6 mA-Seq广泛分布在家蚕基因组中，并且主要集中在调节区和基因体中。对6 mA-Seq和RNA-Seq的综合分析表明，家蚕中6 mA甲基化与低表达基因优先相关，与活跃基因转录负相关，这为DNA 6 mA甲基化对靶基因的调控提供了新的机制。总之，这些数据确定了家蚕中6 mA甲基化，并证明了6 mA信号在控制细胞周期进程中的关键作用。
Increasing knowledge of DNA methylation that occurs on the sixth position of adenine (N6-methyladenine, 6mA) has emerged as a novel epigenetic mark in eukaryotes and plays an important role in regulating gene transcription, DNA replication and repair, transposable activities, and others. Here, we show DNA 6mA methylation is present in Bombyx mori, a lepidopteran model insect, and identify the 6mA methyltransferase, METTL4, and 6mA demethylase, NMAD, which regulate the levels of 6mA in embryogenesis and cultured cells of B. mori. Importantly, RNAi knockdown of METTL4 and NMAD not only induce cell cycle arrest at G1 phase but also result in defects of chromosome alignments at metaphase. We further demonstrate that 6mA methylation is widely distributed across the genome of B. mori by 6mA-Seq and primarily enriched in the regulatory regions as well as gene bodies. Integrated analysis of 6mA-Seq and RNA-Seq reveals that 6mA methylation in B. mori is preferentially related with lowly expressed genes and negatively correlated with active gene transcription, which provides a novel regulatory mechanism of DNA 6mA methylation on target genes. Altogether, these data identify 6mA methylation in B. mori and demonstrate a crucial role of 6mA signaling in controlling cell cycle progression.