Identical sets of methylated and nonmethylated genes in Ciona intestinalis sperm and muscle cells.

Identical sets of methylated and nonmethylated genes in Ciona intestinalis sperm and muscle cells.
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DOI:
10.1186/1756-8935-6-38
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发表时间:
2013-11-11
影响因子:
3.9
通讯作者:
Nakayama A
Nakayama A
中科院分区:
生物学2区
文献类型:
--
作者:
Suzuki MM;Yoshinari A;Obara M;Takuno S;Shigenobu S;Sasakura Y;Kerr AR;Webb S;Bird A;Nakayama A

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基因体甲基化是指基因编码区内的DNA甲基化,它的发现提示了DNA甲基化在活跃转录基因中的作用。在无脊椎动物中,基因体是DNA甲基化的主要目标,并且只有一部分表达基因被修饰。在这里,我们调查的全球水平和分布的5-甲基胞嘧啶(5 mC)的海鞘海鞘的组织变异性。我们发现,早期发育胚胎的整体5 mC含量很高,但在体壁组织中显著减少。我们选择了精子和成年肌肉细胞,分别具有高水平和降低水平的全球5 mC,用于全基因组分析5 mC目标。通过CXXC亲和纯化,然后进行深度测序(CAP-seq)和全基因组亚硫酸氢盐测序(BS-seq),我们指定了每个组织中的身体甲基化和未甲基化基因。令人惊讶的是,身体甲基化和非甲基化的基因组在精子和肌肉细胞中是相同的。我们对微阵列表达数据的分析表明,基因体甲基化与整个发育过程中的广泛表达相关。此外,转基因分析揭示了当整合在不同的基因组位点时,在相同的基因-启动子组合处的对比基因体甲基化。我们的结论是,基因体甲基化不是直接调节组织特异性基因表达的C。好吧我们的研究结果揭示了基因体甲基化的恒定靶向,而与细胞类型无关,它们强调了基因体甲基化与普遍表达的基因之间的相关性。我们的转基因实验表明,启动子并不决定相关基因体的甲基化状态。
The discovery of gene body methylation, which refers to DNA methylation within gene coding region, suggests an as yet unknown role of DNA methylation at actively transcribed genes. In invertebrates, gene bodies are the primary targets of DNA methylation, and only a subset of expressed genes is modified. Here we investigate the tissue variability of both the global levels and distribution of 5-methylcytosine (5mC) in the sea squirt Ciona intestinalis. We find that global 5mC content of early developmental embryos is high, but is strikingly reduced in body wall tissues. We chose sperm and adult muscle cells, with high and reduced levels of global 5mC respectively, for genome-wide analysis of 5mC targets. By means of CXXC-affinity purification followed by deep sequencing (CAP-seq), and genome-wide bisulfite sequencing (BS-seq), we designated body-methylated and unmethylated genes in each tissue. Surprisingly, body-methylated and unmethylated gene groups are identical in the sperm and muscle cells. Our analysis of microarray expression data shows that gene body methylation is associated with broad expression throughout development. Moreover, transgenic analysis reveals contrasting gene body methylation at an identical gene-promoter combination when integrated at different genomic sites. We conclude that gene body methylation is not a direct regulator of tissue specific gene expression in C. intestinalis. Our findings reveal constant targeting of gene body methylation irrespective of cell type, and they emphasize a correlation between gene body methylation and ubiquitously expressed genes. Our transgenic experiments suggest that the promoter does not determine the methylation status of the associated gene body.
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期刊: MOLECULAR CELL
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