John R M, Aparicio S A, Ainscough J F, Arney K L, Khosla S, Hawker K, Hilton K J, Barton S C, Surani M A
Wellcome/CRC Institute of Cancer and Developmental Biology, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
Dev Biol. 2001 Aug 15;236(2):387-99. doi: 10.1006/dbio.2001.0327.
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.
神经母细胞瘤抑制因子（Nnat）是一种印记基因，仅从父本等位基因表达，而母本等位基因沉默且发生甲基化。与其他印记结构域相比，Nnat基因座具有一些独特特征。与大多数成簇组织并协调调控的印记基因不同，Nnat似乎与其他印记基因没有紧密联系。同样不寻常的是，Nnat位于Bc10基因的一个8kb内含子内，该内含子产生双等位基因表达的反义转录本。在20号染色体上的人类NNAT基因座也存在类似的结构组织。Nnat的表达首先在胚胎第8.5天在菱脑节3和5中被检测到，随后，其表达在有丝分裂后神经元组织中广泛存在。使用修饰的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，报告基因转基因揭示了指导组织特异性表达的独特且分散的顺式调控元件，这些元件主要位于赋予等位基因特异性表达区域的上游。
