Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing
Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing
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DOI：
10.1126/science.1228110
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发表时间：
2012-12-14
期刊：
影响因子：
56.9
通讯作者：
Barlow, Denise P.
中科院分区：
文献类型：
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作者：
Latos, Paulina A.;Pauler, Florian M.;Barlow, Denise P.
哺乳动物印迹基因通常与长的非编码(LNC)RNA聚集在一起。三个诱导父母特异性沉默的lncRNAs显示出特征，表明它们的转录比它们的产物更重要。为了测试Airn转录或产物是否沉默Igf2r基因，我们将内源lncRNA缩短到不同的长度。结果排除了剪接和非剪接的Airn lncRNA产物以及Airn核大小和位置在沉默Igf2r中的作用。相反，沉默只需要Igf2r启动子的Airn转录重叠，这在没有抑制性染色质的情况下干扰RNA聚合酶II的招募。这种对lncRNA转录重叠的抑制功能揭示了一种基因沉默机制，这种机制可能广泛存在于哺乳动物基因组中，因为lncRNA转录本丰富。
Mammalian imprinted genes often cluster with long noncoding (lnc) RNAs. Three lncRNAs that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous lncRNA to different lengths. The results excluded a role for spliced and unspliced Airn lncRNA products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn transcriptional overlap of the Igf2r promoter, which interferes with RNA polymerase II recruitment in the absence of repressive chromatin. Such a repressor function for lncRNA transcriptional overlap reveals a gene silencing mechanism that may be widespread in the mammalian genome, given the abundance of lncRNA transcripts.