The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus.
The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus.
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DOI：
10.1016/j.cell.2013.01.015
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发表时间：
2013-02-14
期刊：
影响因子：
64.5
通讯作者：
Kirkegaard K
中科院分区：
文献类型：
--
作者：
Gomez JA;Wapinski OL;Yang YW;Bureau JF;Gopinath S;Monack DM;Chang HY;Brahic M;Kirkegaard K
长链非编码RNA（lncRNAs）作为细胞特异性基因表达的调节因子日益受到重视。在此，一种被称为NeST（Nettoie Salmonella pas Theiler’s；清除沙门氏菌而非泰勒氏病毒）的类似增强子的lncRNA被证明是小鼠病毒易感性位点Tmevp3所赋予的所有表型的原因。该位点是通过SJL/J和B10.S小鼠杂交确定的，包含几个候选基因，包括NeST。源自SJL/J的位点使lncRNA表达更高，在活化的CD8 + T细胞中干扰素 - γ含量增加，泰勒氏病毒持久性增强以及肠道沙门氏菌致病性降低。仅NeST lncRNA的转基因表达就足以赋予SJL/J位点的所有表型。发现NeST RNA与组蛋白H3赖氨酸4甲基转移酶复合物的一个组分WDR5结合，并改变干扰素γ基因座处的组蛋白3甲基化。因此，这种lncRNA调节编码干扰素γ的染色质的表观遗传标记、干扰素 - γ的表达以及对一种病毒和一种细菌病原体的易感性。
Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (Nettoie Salmonella pas Theiler’s; cleanup Salmonella not Theiler’s) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ abundance in activated CD8+ T cells, increased Theiler’s virus persistence and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methytransferase complex, and to alter histone 3 methylation at the interferon gamma locus. Thus, this lncRNA regulates epigenetic marking of IFNγ-encoding chromatin, expression of IFN-γ and susceptibility to a viral and a bacterial pathogen.
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影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
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影响因子：
4.5
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影响因子：
64.8
作者：
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通讯作者：
Merkenschlager, Matthias
影响因子：
64.5
作者：
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通讯作者：
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