Atlas of nascent RNA transcripts reveals high confidence enhancer associated bidirectionals linked with genes across different tissue types

Gene transcription is controlled and modulated by enhancers and promoters. These regions are abundant in non-coding bidirectional RNA transcripts which have been used as a read-out of enhancer and promoter activity. Using nascent RNA transcription data across hundreds of samples, we identified 500,000 regions of bidirectional transcription and linked the transcripts to gene targets. The identified bidirectional and gene pairs are associated with diseases associated SNPs and these pairs are links in 3D genome space. We present these resources as an SQL database which allows for further investigation and understanding of how gene transcription is regulated. WT or p53 -/- MCF10A cells were treated with 10uM nutlin3a and 0.01% DMSO (control) for 3 hours with a total of 2 biological replicates. Nuclei were isolated and PRO-seq libraries were constructed and sequenced.

基因转录由增强子（enhancer）与启动子（promoter）共同调控与修饰。这类调控区域富含非编码双向RNA转录本，此类转录本已被用作反映增强子与启动子活性的检测读出信号。本研究利用覆盖数百个样本的新生RNA转录数据，共鉴定出50万个双向转录区域，并将这些转录本与其对应的基因靶标建立了关联。本次鉴定得到的双向转录区域-基因靶标配对，与疾病相关单核苷酸多态性（SNPs）显著关联，且这些配对关系在三维基因组空间中存在相互连接。我们将本研究构建的相关资源以结构化查询语言（SQL）数据库的形式公开，以供后续研究深入探究并解析基因转录的调控机制。

实验处理方案如下：将野生型（Wild Type, WT）或p53基因敲除（p53 -/-）的MCF10A细胞，分别用10μM nutlin3a与0.01%二甲基亚砜（Dimethyl Sulfoxide, DMSO，对照组）处理3小时，每组设置2次生物学重复。分离细胞核后，构建新生转录组测序（PRO-seq）文库并完成高通量测序。