Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
复制标题
DOI：
10.1038/nature07672
复制
发表时间：
2009-03-12
期刊：
影响因子：
64.8
通讯作者：
Lander, Eric S.
中科院分区：
文献类型：
--
作者：
Guttman, Mitchell;Amit, Ido;Garber, Manuel;French, Courtney;Lin, Michael F.;Feldser, David;Huarte, Maite;Zuk, Or;Carey, Bryce W.;Cassady, John P.;Cabili, Moran N.;Jaenisch, Rudolf;Mikkelsen, Tarjei S.;Jacks, Tyler;Hacohen, Nir;Bernstein, Bradley E.;Kellis, Manolis;Regev, Aviv;Rinn, John L.;Lander, Eric S.
人们越来越认识到，哺乳动物细胞产生数千个大的基因间转录本。然而，这些文字记录的功能意义一直备受争议。虽然有一些很好的例子，但大多数(>；95%)几乎没有证据表明进化保守，并被认为代表转录噪声。在这里，我们报告了一种新的方法来识别大的非编码RNA，使用染色质状态图来发现介于已知蛋白质编码基因座之间的离散转录单位。我们的方法在四种小鼠细胞类型中识别了大约1,600个大的多外显子RNA。与以往的收集形成鲜明对比的是，这些大的介入性非编码RNA(LincRNAs)在其基因组位置、外显子序列和启动子区域显示出强烈的纯化选择，超过95%显示出明显的进化保守性。我们还开发了一种功能基因组学方法，为每个lincRNA分配假定的功能，展示了lincRNAs在从胚胎干细胞多能性到细胞增殖的过程中扮演的各种角色。我们使用基于细胞的分析方法，对100多个lincRNA的预测进行了独立的功能验证。特别是，我们证明了特定的lincRNAs在这些过程中受到关键转录因子的转录调控，如P53、NFκB、Sox2、Oct4(也称为Pou5f1)和Nanog。综上所述，这些结果定义了一组独特的功能lincRNAs，它们高度保守，并与不同的生物过程有关。
There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified ~1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFκB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
登录
查看更多内容
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
10.5
作者：
Rinn, JL;Euskirchen, G;Snyder, M
通讯作者：
Snyder, M
影响因子：
7
作者：
Siepel, A;Bejerano, G;Haussler, D
通讯作者：
Haussler, D
影响因子：
56.9
作者：
Bertone, P;Stolc, V;Snyder, M
通讯作者：
Snyder, M
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ