He Sha, Zhang Hai, Liu Haihua, Zhu Hao
Bioinformatics Section, School of Basic Medical Sciences and Network Center, Southern Medical University, Guangzhou 510515, China.
Bioinformatics. 2015 Jan 15;31(2):178-86. doi: 10.1093/bioinformatics/btu643. Epub 2014 Sep 26.
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.
Website of LongTarget: lncrna.smu.edu.cn, or contact: hao.zhu@ymail.com.
Supplementary data are available at Bioinformatics online.
在哺乳动物细胞中，许多基因通过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）招募到特定的基因组位点，使DNA和染色质甲基化。越来越多的证据表明，许多lncRNA含有能通过形成RNA:DNA三链体与DNA结合的DNA结合基序。lncRNA DNA结合基序和结合位点的鉴定对于解读lncRNA功能以及正确和错误的基因组甲基化至关重要；然而，由于lncRNA可能包含数千个核苷酸，这种鉴定具有挑战性。尚未有对典型lncRNA的计算分析报道。在此，我们报告一种计算方法和程序（LongTarget）来预测lncRNA DNA结合基序和结合位点。我们使用该程序分析了多个反义lncRNA，包括那些控制著名印记簇的lncRNA，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 DNA结合基序和结合位点是可行的。
LongTarget网站：lncrna.smu.edu.cn，或联系：hao.zhu@ymail.com。
补充数据可在《生物信息学》在线获取。
