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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A cluster of oppositely imprinted transcripts at the Gnas locus the distal imprinting region of mouse chromosome 2
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A cluster of oppositely imprinted transcripts at the Gnas locus the distal imprinting region of mouse chromosome 2

机译：在小鼠染色体2的远端印迹区域的Gnas位点上有一个相反印迹的转录物簇

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摘要

Imprinted genes tend to occur in clusters. We have identified a cluster in distal mouse chromosome (Chr) 2, known from early genetic studies to contain both maternally and paternally imprinted, but unspecified, genes. Subse. quently, one was identified as Gnas, which encodes a G protein a subunit, and there is clinical and biochemical evidence that the human homologue GNASI, mutated in patients with Albrigbt hereditary osteodystrophy, is also imprinted. We have used representational difference analysis, based on Parent- of origin methylation differences, to isolate candidate imprinted genes in distal Chr 2 and found two oppositely imprinted genes, Gnasxl and Nesp. Gnasxl determines a variant G protein alpha subunit associated with the trans-Golgi network and Nesp encodes a secreted protein of neuroendocrine tissues. Gnasxl is maternally methylated in genomic DNA and encodes a paternal-specific transcript, whereas Nesp is paternally methylated with maternal-specific expression. Their reciprocal imprinting may offer insight into the distal Chr 2 imprinting phenotypes. Remarkably, Gnasxl, Nesp, and Gnas are all part of the same transcription unit; transcripts for Gnasxl and Nesp are alternatively spliced onto exon 2 of Gnas. This demonstrates an imprinting mechanism in which two oppositely imprinted genes share the same downstream exons.
机译：印迹基因倾向于成簇出现。我们已经在小鼠远端染色体（Chr）2中鉴定出一个簇，这从早期的遗传研究中可以得知，它既包含母本又印刷了父本，但未指定基因。 se因此，人们将其鉴定为编码G蛋白一个亚基的Gnas，并且有临床和生化证据表明，在Albrigbt遗传性骨营养不良患者中突变的人同源GNASI也被印上了印记。我们已经使用了基于母体起源甲基化差异的代表性差异分析来分离Chr 2远端的候选印迹基因，并发现了两个相反的印迹基因Gnasxl和Nesp。 Gnasxl确定与反式高尔基体网络相关的变体G蛋白α亚基，Nesp编码神经内分泌组织的分泌蛋白。 Gnasxl在基因组DNA中被母体甲基化，并编码一个父本特异性的转录本，而Nesp被母本特异性表达的父本甲基化。他们的相互印记可能提供深入了解远端Chr 2印记表型。值得注意的是，Gnasxl，Nesp和Gnas都是同一转录单位的一部分；将Gnasx1和Nesp的转录本选择性地剪接到Gnas的外显子2上。这证明了一种印记机制，其中两个相反的印记基因共享相同的下游外显子。

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