Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells
Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells
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DOI：
10.1016/j.stem.2016.01.024
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发表时间：
2016-05-05
期刊：
影响因子：
23.9
通讯作者：
Shen, Xiaohua
中科院分区：
文献类型：
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作者：
Luo, Sai;Lu, Yuyang;Shen, Xiaohua
在哺乳动物基因组中，与邻近蛋白编码基因相反方向转录的分化的lncRNAs占总lncRNAs的很大比例(接近20%)。通过全基因组分析，我们发现这一类lncRNA的分布与必需的发育调控基因密切相关。在多能细胞中，不同的lncRNA调节附近基因的转录。例如，发散的lncRNA Evx1as促进其邻近基因EVX1的转录，并调节中内胚层分化。在单细胞水平上，早期广泛的Evx1as表达之后是EVX1的快速、高水平转录，支持了Evx1as在促进EVX1转录方面发挥上游作用的观点。在机制上，Evx1as RNA与染色质上的调控位点结合，促进染色质的活跃状态，并与Mediator相互作用。基于我们的分析，我们认为这类数千个未鉴定的lncRNAs的生物学功能可能是从其相邻相邻基因的作用中推断出来的。
Divergent lncRNAs that are transcribed in the opposite direction to nearby protein-coding genes comprise a significant proportion (similar to 20%) of total lncRNAs in mammalian genomes. Through genome-wide analysis, we found that the distribution of this lncRNA class strongly correlates with essential developmental regulatory genes. In pluripotent cells, divergent lncRNAs regulate the transcription of nearby genes. As an example, the divergent lncRNA Evx1as promotes transcription of its neighbor gene, EVX1, and regulates mesendodermal differentiation. At a single-cell level, early broad expression of Evx1as is followed by a rapid, high-level transcription of EVX1, supporting the idea that Evx1as plays an upstream role to facilitate EVX1 transcription. Mechanistically, Evx1as RNA binds to regulatory sites on chromatin, promotes an active chromatin state, and interacts with Mediator. Based on our analyses, we propose that the biological function of thousands of uncharacterized lncRNAs of this class may be inferred from the role of their neighboring adjacent genes.