Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development
Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development
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DOI：
10.1093/hmg/ddp241
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发表时间：
2009-08-15
影响因子：
3.5
通讯作者：
Shen, Lanlan
中科院分区：
文献类型：
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作者：
Waterland, Robert A.;Kellermayer, Richard;Shen, Lanlan
DNA甲基化是否有助于稳定分化的哺乳动物组织中的基因表达模式的问题仍然存在争议。使用全基因组甲基化分析，我们筛选了3757个基因启动子在出生后肝脏发育过程中的甲基化变化，以检验甲基化和表达的发育变化在时间上相关的假设。我们确定了31个获得甲基化的基因和111个从胚胎17.5天到出生后21天失去甲基化的基因。在出生后肝脏中经历甲基化变化的启动子往往与CpG岛无关。在大多数研究的基因中，启动子甲基化的发育变化与表达变化相关，这表明转录失活吸引从头甲基化，并且转录活性可以覆盖DNA甲基化并连续诱导发育低甲基化。这些体内数据清楚地表明了DNA甲基化在哺乳动物分化中的作用，并提供了新的见解，即哺乳动物发育表观遗传学的关键窗口远远超出了早期胚胎发育。
The question of whether DNA methylation contributes to the stabilization of gene expression patterns in differentiated mammalian tissues remains controversial. Using genome-wide methylation profiling, we screened 3757 gene promoters for changes in methylation during postnatal liver development to test the hypothesis that developmental changes in methylation and expression are temporally correlated. We identified 31 genes that gained methylation and 111 that lost methylation from embryonic day 17.5 to postnatal day 21. Promoters undergoing methylation changes in postnatal liver tended not to be associated with CpG islands. At most genes studied, developmental changes in promoter methylation were associated with expression changes, suggesting both that transcriptional inactivity attracts de novo methylation, and that transcriptional activity can override DNA methylation and successively induce developmental hypomethylation. These in vivo data clearly indicate a role for DNA methylation in mammalian differentiation, and provide the novel insight that critical windows in mammalian developmental epigenetics extend well beyond early embryonic development.