Mesh : DNA Methylation Adenine / metabolism Gene Expression Regulation, Fungal Mucorales / genetics metabolism Epigenesis, Genetic Fungal Proteins / genetics metabolism Phylogeny Evolution, Molecular Methyltransferases / metabolism genetics DNA, Fungal / genetics metabolism Mutation

来  源:   DOI:10.1038/s41467-024-50365-2   PDF(Pubmed)

Abstract:
DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.
摘要:
DNAN6-腺嘌呤甲基化(6mA)最近在真核生物中作为表观遗传修饰变得重要。它在高级谱系中的功能,如早期发散真菌(EDF),特别感兴趣。这里,我们研究了6mA在EDF中的生物学意义和进化意义,在6mA的使用中表现出不同的进化模式。对两种显示出极端6mA使用率的Mucorales物种的分析揭示了具有高6mA水平的物种显示出富含高表达基因的对称甲基化。相比之下,具有低6mA水平的物种显示大部分不对称6mA。有趣的是,在整个发育过程中以及对环境线索的响应中,转录组调节与6mA景观的变化有关。此外,我们鉴定了一种EDF特异性甲基转移酶,可能起源于内共生细菌,负责不对称甲基化,而MTA-70甲基化复合物进行对称甲基化。在相应突变体中观察到的不同表型增强了两种类型的6mA在EDF中的关键作用。
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