A comparison of experimental assays and analytical methods for genome-wide identification of active enhancers.

A comparison of experimental assays and analytical methods for genome-wide identification of active enhancers.
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活性增强子全基因组鉴定的实验测定和分析方法的比较。

DOI:
10.1038/s41587-022-01211-7
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发表时间:
2022-07
影响因子:
46.9
通讯作者:
Yu, Haiyuan
Yu, Haiyuan
中科院分区:
工程技术1区
文献类型:
--
作者:
Yao, Li;Liang, Jin;Ozer, Abdullah;Leung, Alden King-Yung;Lis, John T.;Yu, Haiyuan

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越来越多的证据支持的想法,转录模式作为更具体的标识符的活性增强子比组蛋白标记,然而,最佳的策略,以确定活性增强子的实验和计算尚未确定。在这里,我们比较了K562细胞中的13种全基因组RNA测序测定,并表明核运行后的帽选择测定(GRO/PRO-cap)在eRNA检测和活性增强子鉴定中具有优势。我们还引入了一个工具,新生转录起始峰标识符(PINTS),以识别全基因组范围内的活性启动子和增强子,并精确定位5′转录起始位点的精确位置。最后,我们根据在120种细胞和组织类型中检测到的eRNA TSS编制了一份全面的增强子候选纲要,可在https://pints.yulab.org上访问。通过了解最佳可用的检测方法和管道,这种候选增强子的大规模注释将为未来以省时省力的方式选择和表征其功能铺平道路。
Mounting evidence supports the idea that transcriptional patterns serve as more specific identifiers of active enhancers than histone marks; however, the optimal strategy to identify active enhancers both experimentally and computationally has not been determined. Here, we compared 13 genome-wide RNA sequencing assays in K562 cells and showed that the nuclear run-on followed by cap-selection assay (GRO/PRO-cap) has advantages in eRNA detection and active enhancer identification. We also introduced a tool, Peak Identifier for Nascent Transcript Starts (PINTS), to identify active promoters and enhancers genome-wide and pinpoint the precise location of the 5′ transcription start sites. Finally, we compiled a comprehensive enhancer candidate compendium based on the detected eRNA TSSs available in 120 cell and tissue types that can be accessed at https://pints.yulab.org. With the knowledge of the best available assays and pipelines, this large-scale annotation of candidate enhancers will pave the way for selection and characterization of their functions in a time- and labor-efficient manner in the future.
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