Nature2014-06-24 2:34 PM

人类不同细胞类型的转录调控网络 An atlas of active enhancers across human cell types and tissues

论文摘要 

FANTOM5 (即“哺乳动物基因组-5的功能注解”) 是一个大型国际合作项目的第5大阶段,其目标是分析定义每个人类细胞类型的转录调控网络。本期Nature上的两篇Articles论文发表了该项目的一些最新结果。第一篇论文利用FANTOM5项目组的组织和原代细胞样本来定义整个人体中活性的、在活体中双向转录的增强子的一个图集。这些作者发现双向封盖的RNA是活性增强子的一个特征,同时他们还从超过800个人类细胞和组织样本中识别出40,000多个增强子候选物。该增强子图集被用来比较不同细胞类型之间的调控程序和识别与疾病相关的调控性SNP,并且还将成为关于细胞类型特定性增强子的研究工作的一个资源。在第二篇论文中,单分子测序被用来标绘人类和小鼠的转录起始点及它们在一组截然不同的、用于生成迄今最全面哺乳动物基因表达图集的人类和小鼠原代细胞、细胞系和组织中的应用。这些数据为了解涉及不同细胞类型的“开放读框”和启动子提供了大量信息,也为哺乳动物细胞类型特定性转录组提供了有价值的注解。

Abstract 

Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here 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 messenger RNA 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, to identify disease-associated regulatory single nucleotide polymorphisms, and to 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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