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A promoter-level mammalian expression atlas

A promoter-level mammalian expression atlas
A promoter-level mammalian expression atlas
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.
Animals, Atlases as Topic, Cell Line, Cells, Cultured, Cluster Analysis, Conserved Sequence/genetics, Gene Expression Regulation/genetics, Gene Regulatory Networks/genetics, Genes, Essential/genetics, Genome/genetics, Humans, Mice, Molecular Sequence Annotation, Open Reading Frames/genetics, Organ Specificity, Promoter Regions, Genetic/genetics, RNA, Messenger/analysis, Transcription Factors/metabolism, Transcription Initiation Site, Transcription, Genetic/genetics, Transcriptome/genetics
0028-0836
462-470
Forrest, Alistair R. R.
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Kawaji, Hideya
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Rehli, Michael
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Baillie, J. Kenneth
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de Hoon, Michiel J. L.
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Haberle, Vanja
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Lassmann, Timo
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Kulakovskiy, Ivan V.
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Lizio, Marina
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Itoh, Masayoshi
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Andersson, Robin
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Mungall, Christopher J.
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Meehan, Terrence F
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Schmeier, Sebastian
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Bertin, Nicolas
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Jørgensen, Mette
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Dimont, Emmanuel
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Arner, Erik
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Schmidl, Christian
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Schaefer, Ulf
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Medvedeva, Yulia A
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Plessy, Charles
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Vitezic, Morana
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Severin, Jessica
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Semple, Colin A
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Ishizu, Yuri
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Young, Robert S
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Francescatto, Margherita
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Alam, Intikhab
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Albanese, Davide
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Altschuler, Gabriel M
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Arakawa, Takahiro
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Archer, John A C
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Arner, Peter
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Babina, Magda
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Rennie, Sarah
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Balwierz, Piotr J
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Beckhouse, Anthony G
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Pradhan-Bhatt, Swati
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Blake, Judith A
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Blumenthal, Antje
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Bodega, Beatrice
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Bonetti, Alessandro
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Briggs, James
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Brombacher, Frank
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Burroughs, A Maxwell
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Califano, Andrea
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Chen, Yun
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Rackham, Owen J L
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Taylor, Martin S
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FANTOM Consortium and the RIKEN PMI and CLST (DGT)
Forrest, Alistair R. R.
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Kawaji, Hideya
b41d4dc8-fa4b-4f56-b400-9c8f222415a9
Rehli, Michael
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Baillie, J. Kenneth
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de Hoon, Michiel J. L.
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Haberle, Vanja
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Lassmann, Timo
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Kulakovskiy, Ivan V.
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Lizio, Marina
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Itoh, Masayoshi
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Andersson, Robin
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Mungall, Christopher J.
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Meehan, Terrence F
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Schmeier, Sebastian
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Bertin, Nicolas
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Jørgensen, Mette
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Dimont, Emmanuel
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Arner, Erik
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Schmidl, Christian
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Schaefer, Ulf
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Medvedeva, Yulia A
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Plessy, Charles
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Vitezic, Morana
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Severin, Jessica
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Semple, Colin A
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Ishizu, Yuri
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Young, Robert S
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Francescatto, Margherita
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Alam, Intikhab
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Albanese, Davide
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Altschuler, Gabriel M
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Arakawa, Takahiro
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Archer, John A C
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Arner, Peter
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Babina, Magda
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Rennie, Sarah
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Balwierz, Piotr J
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Beckhouse, Anthony G
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Pradhan-Bhatt, Swati
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Blake, Judith A
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Blumenthal, Antje
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Bodega, Beatrice
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Bonetti, Alessandro
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Briggs, James
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Brombacher, Frank
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Burroughs, A Maxwell
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Califano, Andrea
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Chen, Yun
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Rackham, Owen J L
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Taylor, Martin S
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FANTOM Consortium and the RIKEN PMI and CLST (DGT) (2014) A promoter-level mammalian expression atlas. Nature, 507 (7493), 462-470. (doi:10.1038/nature13182).

Record type: Article

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.

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More information

Published date: 26 March 2014
Keywords: Animals, Atlases as Topic, Cell Line, Cells, Cultured, Cluster Analysis, Conserved Sequence/genetics, Gene Expression Regulation/genetics, Gene Regulatory Networks/genetics, Genes, Essential/genetics, Genome/genetics, Humans, Mice, Molecular Sequence Annotation, Open Reading Frames/genetics, Organ Specificity, Promoter Regions, Genetic/genetics, RNA, Messenger/analysis, Transcription Factors/metabolism, Transcription Initiation Site, Transcription, Genetic/genetics, Transcriptome/genetics
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Identifiers

Local EPrints ID: 446685
URI: http://eprints.soton.ac.uk/id/eprint/446685
DOI: doi:10.1038/nature13182
ISSN: 0028-0836
PURE UUID: db3778f3-9925-4d32-91ce-c0c926a5ab10
ORCID for Owen J L Rackham: ORCID iD orcid.org/0000-0002-4390-0872

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Date deposited: 17 Feb 2021 17:35
Last modified: 17 Mar 2024 04:03

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Contributors

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

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