Nature2014-06-24 2:39 PM

人类不同细胞类型的转录调控网络2 A promoter-level mammalian expression atlas


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。


Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.






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