Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.
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启动子分析揭示了人类长的非编码RNA和蛋白质编码基因的全球差异调节。
DOI：
10.1371/journal.pone.0109443
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bajic VB
中科院分区：
文献类型：
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作者：
Alam T;Medvedeva YA;Jia H;Brown JB;Lipovich L;Bajic VB
在全球范围内，蛋白质编码基因的转录调控越来越被人们所了解，但是对于长链非编码RNA（lncRNA）基因，还没有可比较的信息存在，其最近被认为与哺乳动物基因组中的蛋白质编码基因一样多。我们对人类lncRNA和蛋白质编码基因的启动子进行了全基因组比较分析，发现了与转录调控相关的特定遗传和表观遗传特征的全球差异。因此，这两组基因受到单独的转录调控程序，包括明显有利于lncRNA而不是编码基因启动子的不同转录因子（TF）蛋白。我们报告一个特定的签名启动子近端转录调控lncRNA基因，包括几个不同的转录因子结合位点（TFBS）。实验DNase I超敏位点分布与不同人类细胞类型中这些lncRNA TFBS集的活性构型一致。TFBS ChIP-seq数据集证实了我们使用计算方法预测的因子子集的结合事件。对于已知由lncRNA直接调控的几种TF，我们发现它们的推定TFBS在lncRNA启动子处富集，这表明TF和lncRNA可能参与双向反馈环调控网络。因此，细胞能够通过不同的调节途径独立于mRNA水平调节lncRNA表达水平。我们的研究结果还提出了一种可能性，即考虑到历史上依赖于蛋白质编码基因目录来定义活性启动子的染色质状态，将来有必要对这些染色质特征谱进行修订，以纳入表达的lncRNA基因。
Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
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通讯作者：
Gustincich, Stefano
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