Deep sequencing reveals a novel class of bidirectional promoters associated with neuronal genes.
Deep sequencing reveals a novel class of bidirectional promoters associated with neuronal genes.
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DOI：
10.1186/1471-2164-15-457
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发表时间：
2014-06-10
期刊：
影响因子：
4.4
通讯作者：
Khaitovich P
中科院分区：
文献类型：
--
作者：
Hu HY;He L;Khaitovich P
在给定组织中表达的转录本的全面注释是理解形成转录组的调控和功能途径的关键一步。在这里，我们基于在出生后发育的不同阶段收集的大约3亿条链特异性RNA序列（RNA-seq）读数重建了人类前额叶皮层（PFC）的累积转录组。我们发现超过50%的重建转录本代表新的转录组元件，包括8，343个新的外显子和注释编码基因的外显子延伸，11，217个新的反义转录本和29，541个新的基因间转录本或其片段，显示长非编码RNA（lncRNA）的典型特征。我们的分析进一步导致了一类新型双向启动子（NBiP）的令人惊讶的发现，其驱动mRNA和新型lncRNA对的趋异转录，并显示出一组独特的序列和表观遗传特征。与已知的双向和单向启动子相反，NBiPs与参与神经元功能的基因密切相关，并受神经元相关转录因子的调节。综上所述，我们的结果表明，大部分的人类转录组仍然是未知的。NBiPs的独特序列和表观遗传特征，以及它们与神经元基因的特异性关联，进一步表明存在对人脑特异性的调节途径。本文的在线版本（doi：10.1186/1471-2164-15-457）包含补充材料，可供授权用户使用。
Comprehensive annotation of transcripts expressed in a given tissue is a critical step towards the understanding of regulatory and functional pathways that shape the transcriptome. Here, we reconstructed a cumulative transcriptome of the human prefrontal cortex (PFC) based on approximately 300 million strand-specific RNA sequence (RNA-seq) reads collected at different stages of postnatal development. We find that more than 50% of reconstructed transcripts represent novel transcriptome elements, including 8,343 novel exons and exon extensions of annotated coding genes, 11,217 novel antisense transcripts and 29,541 novel intergenic transcripts or their fragments showing canonical features of long non-coding RNAs (lncRNAs). Our analysis further led to a surprising discovery of a novel class of bidirectional promoters (NBiPs) driving divergent transcription of mRNA and novel lncRNA pairs and displaying a distinct set of sequence and epigenetic features. In contrast to known bidirectional and unidirectional promoters, NBiPs are strongly associated with genes involved in neuronal functions and regulated by neuron-associated transcription factors. Taken together, our results demonstrate that large portions of the human transcriptome remain uncharacterized. The distinct sequence and epigenetic features of NBiPs, as well as their specific association with neuronal genes, further suggest existence of regulatory pathways specific to the human brain. The online version of this article (doi:10.1186/1471-2164-15-457) contains supplementary material, which is available to authorized users.
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影响因子：
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