A promoter-level mammalian expression atlas

Alistair R R Forrest, Hideya Kawaji, Michael Rehli, J Kenneth Baillie, Michiel J L de Hoon, Vanja Haberle, Timo Lassmann, Ivan V Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Christopher J Mungall, Terrence F Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner, Christian Schmidl, Ulf SchaeferYulia A Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A Semple, Yuri Ishizu, Robert S Young, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel M Altschuler, Takahiro Arakawa, John A C Archer, Peter Arner, Magda Babina, Sarah Rennie, Piotr J Balwierz, Anthony G Beckhouse, Swati Pradhan-Bhatt, Judith A Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A Maxwell Burroughs, Hai Fang, Julian Gough, David A de Lima Morais, Owen J L Rackham, FANTOM Consortium and the RIKEN PMI and CLST (DGT)

Research output: Contribution to journalArticle (Academic Journal)peer-review

973 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)462-70
Number of pages9
JournalNature
Volume507
Issue number7493
DOIs
Publication statusPublished - 27 Mar 2014

Keywords

  • Animals
  • Atlases as Topic
  • Cell Line
  • Cells, Cultured
  • Cluster Analysis
  • Conserved Sequence
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genes, Essential
  • Genome
  • Humans
  • Mice
  • Molecular Sequence Annotation
  • Open Reading Frames
  • Organ Specificity
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Transcription Factors
  • Transcription Initiation Site
  • Transcription, Genetic
  • Transcriptome

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