Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation.
Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation.
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DOI：
10.1101/gad.310367.117
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发表时间：
2018-02-01
影响因子：
10.5
通讯作者：
Stark A
中科院分区：
文献类型：
--
作者：
Catarino RR;Stark A
Catarino 和 Stark 的这篇综述讨论了对增强子功能的机制方面的最新见解。它涵盖了基于染色质特征的增强子预测及其通过功能报告分析和内源 DNA 扰动进行识别的最新进展。增强子是指导细胞类型特异性转录的重要基因组调控元件。它们在发育和疾病过程中发挥着关键作用，它们的鉴定和功能表征长期以来一直是科学兴趣的焦点。新一代测序和基于成簇规则间隔短回文重复 (CRISPR)/Cas9 的基因组编辑的出现彻底改变了我们研究增强子生物学的方法。在这篇综述中，我们介绍了基于染色质特征的增强子预测及其通过功能报告分析和内源 DNA 扰动进行识别的最新进展。我们讨论后两种方法提供了不同且互补的见解，特别是在评估增强子的充分性和转录激活的必要性方面。此外，我们还讨论了最近对增强子功能机制方面的见解，包括关于辅因子需求和翻译后组蛋白修饰（例如组蛋白 H3 Lys4 (H3K4me1) 的单甲基化）的作用的发现。最后，我们调查了这些方法如何增进我们对启动子特异性和转录爆发方面的转录调控的理解，并提供了涵盖悬而未决的问题和有希望的发展的前景。
This review by Catarino and Stark discusses recent insights into mechanistic aspects of enhancer functions. It covers recent developments in the prediction of enhancers based on chromatin characteristics and their identification by functional reporter assays and endogenous DNA perturbations. Enhancers are important genomic regulatory elements directing cell type-specific transcription. They assume a key role during development and disease, and their identification and functional characterization have long been the focus of scientific interest. The advent of next-generation sequencing and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based genome editing has revolutionized the means by which we study enhancer biology. In this review, we cover recent developments in the prediction of enhancers based on chromatin characteristics and their identification by functional reporter assays and endogenous DNA perturbations. We discuss that the two latter approaches provide different and complementary insights, especially in assessing enhancer sufficiency and necessity for transcription activation. Furthermore, we discuss recent insights into mechanistic aspects of enhancer function, including findings about cofactor requirements and the role of post-translational histone modifications such as monomethylation of histone H3 Lys4 (H3K4me1). Finally, we survey how these approaches advance our understanding of transcription regulation with respect to promoter specificity and transcriptional bursting and provide an outlook covering open questions and promising developments.
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DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
4
作者：
Barolo, Scott
通讯作者：
Barolo, Scott
影响因子：
5.3
作者：
Anandhakumar, Jayamani;Moustafa, Yara W.;Gross, David S.
通讯作者：
Gross, David S.
影响因子：
16.6
作者：
Andersson, Robin;Andersen, Peter Refsing;Sandelin, Albin
通讯作者：
Sandelin, Albin
影响因子：
4
作者：
Andersson, Robin
通讯作者：
Andersson, Robin