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在高通量检测和基因组编辑时代塑造模糊的增强子。

Shaping the nebulous enhancer in the era of high-throughput assays and genome editing.

机构信息

Department of Biomedical Engineering.

Department of Computer Science and Engineering, The Chinese University of Hong Kong, Hong Kong.

出版信息

Brief Bioinform. 2020 May 21;21(3):836-850. doi: 10.1093/bib/bbz030.

DOI:10.1093/bib/bbz030
PMID:30895290
Abstract

Since the 1st discovery of transcriptional enhancers in 1981, their textbook definition has remained largely unchanged in the past 37 years. With the emergence of high-throughput assays and genome editing, which are switching the paradigm from bottom-up discovery and testing of individual enhancers to top-down profiling of enhancer activities genome-wide, it has become increasingly evidenced that this classical definition has left substantial gray areas in different aspects. Here we survey a representative set of recent research articles and report the definitions of enhancers they have adopted. The results reveal that a wide spectrum of definitions is used usually without the definition stated explicitly, which could lead to difficulties in data interpretation and downstream analyses. Based on these findings, we discuss the practical implications and suggestions for future studies.

摘要

自 1981 年首次发现转录增强子以来,在过去的 37 年中,其教科书定义在很大程度上保持不变。随着高通量检测和基因组编辑技术的出现,这种技术正在将研究范式从逐个发现和检测增强子的“自下而上”方法转变为对整个基因组中增强子活性进行“自上而下”的分析,越来越多的证据表明,这一经典定义在不同方面留下了大量的灰色地带。在这里,我们调查了一组有代表性的最近的研究文章,并报告了他们所采用的增强子定义。结果表明,通常使用的定义范围很广,但没有明确说明定义,这可能导致数据解释和下游分析困难。基于这些发现,我们讨论了未来研究的实际意义和建议。

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引用本文的文献

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Molecules. 2021 Feb 5;26(4):828. doi: 10.3390/molecules26040828.
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Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.Fra-1 通过与远端增强子结合来调控其靶基因,而不在三阴性乳腺癌中对染色质结构施加主要控制。
Nucleic Acids Res. 2021 Mar 18;49(5):2488-2508. doi: 10.1093/nar/gkab053.
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Enhancer prediction in the human genome by probabilistic modelling of the chromatin feature patterns.
通过对染色质特征模式的概率建模来预测人类基因组中的增强子。
BMC Bioinformatics. 2020 Jul 20;21(1):317. doi: 10.1186/s12859-020-03621-3.