Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.
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.
转录调控控制着构成哺乳动物的数百种细胞类型的多样性、发育途径和空间组织。我们使用单分子 cDNA 测序技术，绘制了人类和小鼠原代细胞、细胞系和组织中转录起始位点（TSS）及其使用情况的图谱，从而全面概述了哺乳动物在人体中的基因表达情况。我们发现，很少有基因是真正的“管家基因”，而许多哺乳动物启动子是由几个紧密分离的 TSS 组成的复合实体，具有独立的细胞类型特异性表达谱。特定于不同细胞类型的 TSS 以不同的速度进化，而广泛表达基因的启动子则是最保守的。基于启动子的表达分析揭示了定义细胞状态的关键转录因子，并将它们与结合位点基序联系起来。通过共表达和样本本体论富集分析，可以预测鉴定出的新型转录本的功能。哺乳动物基因组 5（FANTOM5）项目的功能注释提供了全面的哺乳动物细胞类型特异性转录组的表达谱和功能注释，在生物医学研究中有广泛的应用。
