LongTarget: a tool to predict lncRNA DNA-binding motifs and binding sites via Hoogsteen base-pairing analysis
LongTarget: a tool to predict lncRNA DNA-binding motifs and binding sites via Hoogsteen base-pairing analysis
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DOI：
10.1093/bioinformatics/btu643
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发表时间：
2015-01-15
期刊：
影响因子：
5.8
通讯作者：
Zhu, Hao
中科院分区：
文献类型：
--
作者：
He, Sha;Zhang, Hai;Zhu, Hao
动机：在哺乳动物细胞中，许多基因因基因组甲基化而沉默。DNA甲基转移酶和多梳抑制复合物都缺乏序列特异性DNA结合基序，它们被长链非编码RNA（lncRNA）募集到特定的基因组位点以甲基化DNA和染色质。越来越多的证据表明，许多lncRNA含有DNA结合基序，可以通过形成RNA：DNA三链体与DNA结合。lncRNA DNA结合基序和结合位点的鉴定对于破译lncRNA功能以及正确和错误的基因组甲基化是必不可少的;然而，这种鉴定是具有挑战性的，因为lncRNA可能含有数千个核苷酸。没有典型lncRNA的计算分析报告。在这里，我们报告的计算方法和程序（LongTarget）预测lncRNA的DNA结合基序和结合位点。我们用这个程序来分析多个反义lncRNA，包括那些控制众所周知的印迹集群，并获得了与实验观察和表观遗传标记一致的结果。这些结果表明，在全基因组范围内预测许多lncRNA的DNA结合基序和结合位点是可行的
Motivation: In mammalian cells, many genes are silenced by genome methylation. DNA methyltransferases and polycomb repressive complexes, which both lack sequence-specific DNA-binding motifs, are recruited by long non-coding RNA (lncRNA) to specific genomic sites to methylate DNA and chromatin. Increasing evidence indicates that many lncRNAs contain DNA-binding motifs that can bind to DNA by forming RNA:DNA triplexes. The identification of lncRNA DNA-binding motifs and binding sites is essential for deciphering lncRNA functions and correct and erroneous genome methylation; however, such identification is challenging because lncRNAs may contain thousands of nucleotides. No computational analysis of typical lncRNAs has been reported. Here, we report a computational method and program (LongTarget) to predict lncRNA DNA-binding motifs and binding sites. We used this program to analyse multiple antisense lncRNAs, including those that control well-known imprinting clusters, and obtained results agreeing with experimental observations and epigenetic marks. These results suggest that it is feasible to predict many lncRNA DNA-binding motifs and binding sites genome-wide