Imprinted expression of Neuronatin from modified BAC transgenes reveals regulation by distinct and distant enhancers
Imprinted expression of Neuronatin from modified BAC transgenes reveals regulation by distinct and distant enhancers
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DOI：
10.1006/dbio.2001.0327
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发表时间：
2001-08-15
影响因子：
2.7
通讯作者：
Surani, MA
中科院分区：
文献类型：
--
作者：
John, RM;Aparicio, SAJR;Surani, MA
Neuronatin(NNAT)是一种印迹基因，它只在父亲的等位基因中表达，而母亲的等位基因是沉默的和甲基化的。与其他印迹结构域相比，NNAT基因座显示出一些独特的特征。与大多数印迹基因不同，NNAT似乎与其他印迹基因没有紧密的联系。同样不同寻常的是，NNAT位于BC10基因的8kb内含子内，该内含子产生双等位表达的反义转录本。在20号染色体上的人类NNAT基因座上也有类似的组织保守。NNAT首先在3号和5号菱形染色体的E8.5处检测到表达，随后在有丝分裂后神经元组织中广泛表达。使用改进的BAC转基因，我们发现NNAT在异位位点的印记表达最多需要基因周围80kb的区域。此外，报告转基因揭示了不同和分散的顺式调控元件，这些元件指导组织特异性表达，这些元件主要位于赋予等位基因特异性表达的区域的上游。(C)2001年学术出版社。
Neuronatin (Nnat) is an imprinted gene that is expressed exclusively from the paternal allele while the maternal allele is silent and methylated. The Nnat locus exhibits some unique features compared with other imprinted domains. Unlike the majority of imprinted genes, which are organised in clusters and coordinately regulated, Nnat does not appear to be closely linked to other imprinted genes. Also unusually, Nnat is located within an 8-kb intron of the Bc10 gene, which generates a biallelically expressed, antisense transcript. A similar organisation is conserved at the human NNAT locus on chromosome 20. Nnat expression is first detected at E8.5 in rhombomeres 3 and 5, and subsequently, expression is widespread within postmitotic neuronal tissues. Using modified BAC transgenes, we show that imprinted expression of Nnat at ectopic sites requires, at most, an 80-kb region around the gene. Furthermore, reporter transgenes reveal distinct and dispersed cis-regulatory elements that direct tissue-specific expression and these are predominantly upstream of the region that confers allele-specific expression. (C) 2001 Academic Press.