Silencing and transcriptional properties of the imprinted Airn ncRNA are independent of the endogenous promoter
Silencing and transcriptional properties of the imprinted Airn ncRNA are independent of the endogenous promoter
复制标题
印记 Airn ncRNA 的沉默和转录特性独立于内源启动子
DOI：
10.1038/emboj.2008.239
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Denise P. Barlow
中科院分区：
文献类型：
--
作者：
Stefan H. Stricker;L. Steenpass;F. Pauler;Federica Santoro;Paulina A Latos;R. Huang;Martha V. Koerner;Mathew A Sloane;Katarzyna E. Warczok;Denise P. Barlow
Airn macro ncRNA是Igf2r印迹基因簇中印迹表达的主要调节因子，在Igf2r印迹基因簇中，Airn macro ncRNA使三个顺式侧翼基因沉默。Airn转录显示出通常被视为启动子特异性的不寻常特征，例如转录后加工受损和宏观尺寸。Airn转录物长108 kb，主要是未剪接和核定位的，只有少数被剪接和输出。在这里，我们通过删除Airn ncRNA启动子并用组成型强或弱启动子替换，显示剪接抑制和终止以及沉默活性由外源启动子的强Airn表达维持。这表明所有功能区域都位于Airn转录本内。母亲的印记控制元件（ICE）的DNA甲基化限制了Airn表达的父亲的等位基因，我们还表明，一个强大的活性启动子是必要的，以保持非甲基化状态的父亲ICE。因此，Airn表达不仅诱导侧翼mRNA基因的沉默，而且保护ICE的父系拷贝免于从头甲基化。
The Airn macro ncRNA is the master regulator of imprinted expression in the Igf2r imprinted gene cluster where it silences three flanking genes in cis. Airn transcription shows unusual features normally viewed as promoter specific, such as impaired post‐transcriptional processing and a macro size. The Airn transcript is 108 kb long, predominantly unspliced and nuclear localized, with only a minority being variably spliced and exported. Here, we show by deletion of the Airn ncRNA promoter and replacement with a constitutive strong or weak promoter that splicing suppression and termination, as well as silencing activity, are maintained by strong Airn expression from an exogenous promoter. This indicates that all functional regions are located within the Airn transcript. DNA methylation of the maternal imprint control element (ICE) restricts Airn expression to the paternal allele and we also show that a strong active promoter is required to maintain the unmethylated state of the paternal ICE. Thus, Airn expression not only induces silencing of flanking mRNA genes but also protects the paternal copy of the ICE from de novo methylation.
影响因子：
4.6
作者：
A. Wutz;H. Theussl;J. Dausman;R. Jaenisch;D. Barlow;E. Wagner
通讯作者：
A. Wutz;H. Theussl;J. Dausman;R. Jaenisch;D. Barlow;E. Wagner
影响因子：
56.9
作者：
PFEIFER, GP;STEIGERWALD, SD;RIGGS, AD
通讯作者：
RIGGS, AD