Comparative genome analysis of the mouse imprinted gene IMPACT and its nonimprinted human homolog IMPACT:: Toward the structural basis for species-specific imprinting
Comparative genome analysis of the mouse imprinted gene IMPACT and its nonimprinted human homolog IMPACT:: Toward the structural basis for species-specific imprinting
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DOI：
10.1101/gr.139200
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发表时间：
2000-12-01
期刊：
影响因子：
7
通讯作者：
Ito, T
中科院分区：
文献类型：
--
作者：
Okamura, K;Hagiwara-Takeuchi, Y;Ito, T
Mouse Impact是一个父系表达的基因，编码一种功能未知的进化保守蛋白。在这里，我们确定了IMPACT，人类同源的影响，在染色体18q11.2-12.1，一个区域同线的小鼠影响基因座。IMPACT在两个信息胎儿的脑和各种组织中以及在一个信息成人的外周血中双等位基因表达。为了揭示两个物种之间等位基因表达差异的结构基础，我们阐明了小鼠Impact（~ 38 kb）和人IMPACT（~ 30 kb）的完整基因组序列。序列比较显示，这两个基因共享一个保守的外显子-内含子组织，但承担显着不同的CpG岛。小鼠岛位于第一内含子中，含有特征性的串联重复序列。此外，这个岛作为一个差异甲基化的区域（DMR）组成的高甲基化的母系等位基因和非甲基化的父系等位基因。有趣的是，这个内含子岛在非印记的人类IMPACT中缺失;其唯一的CpG岛跨越第一外显子，缺乏任何明显的重复，并且逃避了两条染色体上的甲基化。这些结果表明，内含子DMR祈祷的影响印记的作用。
Mouse Impact is a paternally expressed gene encoding an evolutionarily conserved protein of unknown function. Here we identified IMPACT, the human homolog of Impact, on chromosome 18q11.2-12.1, a region syntenic to the mouse Impact locus. IMPACT was expressed biallelically in brain and in various tissues from two informative Fetuses and in peripheral blood from an informative adult. To reveal the structural basis for the difference in allelic expression between the two species, we elucidated complete genome sequences For both mouse Impact (-38 kb) and human IMPACT (-30 kb). Sequence comparison revealed that the two genes share a well-conserved exon-intron organization but bear significantly different CpG islands. The mouse island lies in the first intron and contains characteristic tandem repeats. Furthermore, this island serves as a differentially methylated region (DMR) consisting of a hypermethylated maternal allele and an unmethylated paternal allele. Intriguingly, this intronic island is missing from the nonimprinted human IMPACT; whose sole CpG island spans the First exon, lacks any apparent repeats, and escapes methylation on both chromosomes. These results suggest that the intronic DMR prays a role in the imprinting of Impact.