Imprinted silencing of Slc22a2 and Slc22a3 does not need transcriptional overlap between Igf2r and Air
Imprinted silencing of Slc22a2 and Slc22a3 does not need transcriptional overlap between Igf2r and Air
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DOI：
10.1093/emboj/cdg341
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发表时间：
2003-07-15
期刊：
影响因子：
11.4
通讯作者：
Barlow, DP
中科院分区：
文献类型：
--
作者：
Sleutels, F;Tjon, G;Barlow, DP
三个印迹基因（Igf2r，Slc22a2和Slc22a3）的父本等位基因的沉默需要与其中一个（Igf2r）的启动子重叠的Air RNA的顺式表达。空气是一种非编码RNA，其作用方式尚不清楚。我们测试了Igf2r启动子的作用以及Igf2r和Air之间的转录重叠在该簇中沉默中的作用。我们分析了印迹表达的小鼠中，其中Igf2r启动子被替换为胸苷激酶启动子，保留了与空气的转录重叠，并在小鼠中与缺失的Igf2r启动子，缺乏任何转录重叠与空气。Air、Slc22a2和Slc22a3的印记沉默由替换启动子维持，并且也在不存在与Air的转录重叠的情况下维持。这些结果排除了Igf2r启动子和Igf2r与Air之间的转录重叠在沉默Air、Slc22a2和Slc22a3中的作用。虽然这些结果并没有完全排除双链RNA沉默机制的作用，但它们确实允许Air RNA具有内在顺式沉默特性的可能性。
Silencing of the paternal allele of three imprinted genes (Igf2r, Slc22a2 and Slc22a3) requires cis expression of the Air RNA that overlaps the promoter of one of them (Igf2r). Air is a non-coding RNA whose mode of action is unknown. We tested the role of the Igf2r promoter and the role of transcriptional overlap between Igf2r and Air in silencing in this cluster. We analyzed imprinted expression in mice in which the Igf2r promoter is replaced by a thymidine kinase promoter that preserves a transcription overlap with Air, and in mice with a deleted Igf2r promoter that lack any transcriptional overlap with Air. Imprinted silencing of Air, Slc22a2 and Slc22a3 is maintained by the replacement promoter and also in the absence of transcriptional overlap with Air. These results exclude a role for the Igf2r promoter and for transcriptional overlap between Igf2r and Air in silencing Air, Slc22a2 and Slc22a3. Although these results do not completely exclude a role for a double-stranded RNA silencing mechanism, they do allow the possibility that the Air RNA has intrinsic cis silencing properties.