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DNA methylation enables transposable element-driven genome expansion.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-08-11 , DOI: 10.1073/pnas.1921719117
Wanding Zhou 1, 2 , Gangning Liang 3 , Peter L Molloy 4 , Peter A Jones 5
Affiliation  

Multicellular eukaryotic genomes show enormous differences in size. A substantial part of this variation is due to the presence of transposable elements (TEs). They contribute significantly to a cell’s mass of DNA and have the potential to become involved in host gene control. We argue that the suppression of their activities by methylation of the C–phosphate–G (CpG) dinucleotide in DNA is essential for their long-term accommodation in the host genome and, therefore, to its expansion. An inevitable consequence of cytosine methylation is an increase in C-to-T transition mutations via deamination, which causes CpG loss. Cytosine deamination is often needed for TEs to take on regulatory functions in the host genome. Our study of the whole-genome sequences of 53 organisms showed a positive correlation between the size of a genome and the percentage of TEs it contains, as well as a negative correlation between size and the CpG observed/expected (O/E) ratio in both TEs and the host DNA. TEs are seldom found at promoters and transcription start sites, but they are found more at enhancers, particularly after they have accumulated C-to-T and other mutations. Therefore, the methylation of TE DNA allows for genome expansion and also leads to new opportunities for gene control by TE-based regulatory sites.



中文翻译:

DNA甲基化可实现转座因子驱动的基因组扩展。

多细胞真核基因组显示出巨大的差异。这种变化的很大一部分是由于转座因子(TEs)的存在。它们对细胞的DNA质量有重要贡献,并有可能参与宿主基因的控制。我们认为,通过DNA中的C-磷酸-G(CpG)二核苷酸甲基化抑制其活性对于它们在宿主基因组中的长期适应以及因此对其扩展至关重要。胞嘧啶甲基化的必然结果是通过脱氨基作用导致C到T转换突变的增加,这会导致CpG丢失。TE经常需要胞嘧啶脱氨才能发挥宿主基因组中的调节功能。我们对53种生物的全基因组序列进行的研究显示,基因组大小与所含TEs百分比之间呈正相关,而在大小与CpG观察/预期(O / E)比之间呈负相关。 TE和宿主DNA均如此。很少在启动子和转录起始位点发现TEs,但在增强子中发现更多,特别是在它们积累了C-to-T和其他突变之后。因此,TE DNA的甲基化允许基因组扩展,并且还为基于TE的调控位点带来了新的基因控制机会。特别是在它们积累了C-to-T和其他突变之后。因此,TE DNA的甲基化允许基因组扩展,并且还为基于TE的调控位点带来了新的基因控制机会。特别是在它们积累了C-to-T和其他突变之后。因此,TE DNA的甲基化允许基因组扩展,并且还为基于TE的调控位点带来了新的基因控制机会。

更新日期:2020-08-11
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