An atlas of active enhancers across human cell types and tissues.

An atlas of active enhancers across human cell types and tissues.
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DOI:
10.1038/nature12787
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发表时间:
2014-03-27
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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增强子控制高等真核生物中基因表达的正确时间和细胞类型特异性激活。了解它们的特性、调节活性和靶点对于理解分化和稳态的调节至关重要。我们使用覆盖大多数人体组织和细胞类型的FANTOM 5样本组来产生活性体内转录增强子的图谱。我们发现,增强子与CpG贫乏的mRNA启动子共享特性,但产生双向的、外泌体敏感的、相对较短的未剪接RNA,其产生与增强子活性密切相关。该图谱用于以前所未有的深度比较不同细胞之间的调控程序,识别疾病相关的调控单核苷酸多态性,并对细胞类型特异性和普遍存在的增强子进行分类。我们进一步探讨增强子冗余的效用,这解释了基因表达强度,而不是表达模式。在线FANTOM 5增强子图谱是研究细胞类型特异性增强子和基因调控的独特资源。
Enhancers control the correct temporal and cell type-specific activation of gene expression in higher eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. We use the FANTOM5 panel of samples covering the majority of human tissues and cell types to produce an atlas of active, in vivo transcribed enhancers. We show that enhancers share properties with CpG-poor mRNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, identify disease-associated regulatory single nucleotide polymorphisms, and classify cell type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell type-specific enhancers and gene regulation.
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