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Regulated transcr-ption 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 transcr-ption start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expressi0n 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 expressi0n profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expressi0n analysis reveals key transcr-ption factors defining cell states and 1inks them to binding-site motifs. The functions of identified novel transcr-pts can be predicted by coexpressi0n and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expressi0n profiles and functional annotation of mammalian cell-type-specific transcr-ptomes with wide applications in biomedical research.
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