Delta-like and Gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12
Delta-like and Gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12
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DOI：
10.1016/s0960-9822(00)00704-1
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发表时间：
2000-09-21
期刊：
影响因子：
9.2
通讯作者：
Ferguson-Smith, AC
中科院分区：
文献类型：
--
作者：
Takada, S;Tevendale, M;Ferguson-Smith, AC
小鼠12号染色体的远端部分是印记的。然而，迄今为止，Gt 12是在12号染色体上鉴定的唯一印记基因。Gtl 2编码多个选择性剪接的转录物，没有明显的开放阅读框架。使用具有12号染色体（M12）的母本或父本单亲二体性的孕体，我们发现Gt 12从母本等位基因表达，并在沉默的父本等位基因的5'端甲基化。在Gt 12上游80 kb处鉴定出与Notch信号传导途径中涉及的基因具有同源性的一个印迹基因，Delta样（Dlk），Dlk基因在胚胎和胎盘中均由父本等位基因表达，但在两个亲本等位基因上Dlk基因的CpG岛启动子完全未甲基化，而是在活跃的Dlk等位基因的最后一个外显子中鉴定出父本甲基化区域。该结构域中的邻近性、相互印记和甲基化让人想起小鼠7号染色体上协同调节的Igf 2-H19印记结构域，与H19和Igf 2一样，Gtl 2和Dlk在整个发育过程中在相同组织中共表达，但不是在出生后。这些结果对印迹结构域的调控、功能和进化具有重要意义。
The distal portion of mouse chromosome 12 is imprinted. to date, however, Gtl2 is the only imprinted gene identified on chromosome 12. Gtl2 encodes multiple alternatively spliced transcripts with no apparent open reading frame. Using conceptuses with maternal or paternal uniparental disomy for chromosome 12 (UPD12), we found that Gtl2 is expressed from the maternal allele and methylated at the 5' end of the silent paternal allele, A reciprocally imprinted gene, Delta-like (Dlk), with homology to genes involved in the Notch signalling pathway was identified 80 kb upstream of Gtl2, Dlk was expressed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both parental alleles, Rather, a paternally methylated region was identified in the last exon of the active Dlk allele. The proximity, reciprocal imprinting and methylation in this domain are reminiscent of the co-ordinately regulated Igf2-H19 imprinted domain on mouse chromosome 7, Like H19 and Igf2, Gtl2 and Dlk were found to be co-expressed in the same tissues throughout development, though not after birth. These results have implications for the regulation, function and evolution of imprinted domains.