Suzuki Miho M, Kerr Alastair R W, De Sousa Dina, Bird Adrian
The Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Michael Swann Building, The King's Buildings, Edinburgh EH9 3JR, UK.
Genome Res. 2007 May;17(5):625-31. doi: 10.1101/gr.6163007. Epub 2007 Apr 9.
DNA is methylated at the dinucleotide CpG in genomes of a wide range of plants and animals. Among animals, variable patterns of genomic CpG methylation have been described, ranging from undetectable levels (e.g., in Caenorhabditis elegans) to high levels of global methylation in the vertebrates. The most frequent pattern in invertebrate animals, however, is mosaic methylation, comprising domains of methylated DNA interspersed with unmethylated domains. To understand the origin of mosaic DNA methylation patterns, we examined the distribution of DNA methylation in the Ciona intestinalis genome. Bisulfite sequencing and computational analysis revealed methylated domains with sharp boundaries that strongly colocalize with approximately 60% of transcription units. By contrast, promoters, intergenic DNA, and transposons are not preferentially targeted by DNA methylation. Methylated transcription units include evolutionarily conserved genes, whereas the most highly expressed genes preferentially belong to the unmethylated fraction. The results lend support to the hypothesis that CpG methylation functions to suppress spurious transcriptional initiation within infrequently transcribed genes.
在广泛的动植物基因组中，DNA在二核苷酸CpG处发生甲基化。在动物中，已描述了基因组CpG甲基化的多种模式，范围从检测不到的水平（例如在秀丽隐杆线虫中）到脊椎动物中的高水平全基因组甲基化。然而，无脊椎动物中最常见的模式是镶嵌甲基化，即甲基化DNA结构域与未甲基化结构域相间分布。为了了解镶嵌DNA甲基化模式的起源，我们研究了海鞘基因组中DNA甲基化的分布。亚硫酸氢盐测序和计算分析揭示了具有清晰边界的甲基化结构域，这些结构域与约60%的转录单元高度共定位。相比之下，启动子、基因间DNA和转座子并非DNA甲基化的优先靶向对象。甲基化的转录单元包括进化上保守的基因，而表达最高的基因优先属于未甲基化部分。这些结果支持了这样一种假说，即CpG甲基化的功能是抑制不常转录基因内的异常转录起始。
