Artigo Acesso aberto Revisado por pares

A promoter-level mammalian expression atlas

2014; Nature Portfolio; Volume: 507; Issue: 7493 Linguagem: Inglês

10.1038/nature13182

ISSN

1476-4687

Autores

Alistair R. R. Forrest, Hideya Kawaji, Michael Rehli, J. Kenneth Baillie, Michiel de Hoon, Vanja Haberle, Timo Lassmann, Ivan V. Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Chris Mungall, Terrence F. Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Peter Arner, Christian Schmidl, Ulf Schaefer, Yulia A. Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. Semple, Yuri Ishizu, Robert S. Young, Margherita Francescatto, Intikhab Álam, Davide Albanese, Gabriel M. Altschule, 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, Andrea Califano, Carlo Vittorio Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans Clevers, Emiliano Dalla, Carrie Davis, Michael Detmar, Alexander D. Diehl, Taeko Dohi, Finn Drabløs, Albert S.B. Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C. Farach‐Carson, Geoffrey J. Faulkner, Alexander V. Favorov, Malcolm E Fisher, Martin C. Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furuno, Jun Furusawa, Teunis B. H. Geijtenbeek, Andrew P. Gibson, T Gingeras, Dan Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J Hitchens, Shannan J. Ho Sui, Oliver Hofmann, Ilka Hoof, Fumi Hori, Łukasz Huminiecki, Kei Iida, Tomokatsu Ikawa, Boris R. Janković, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumił Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi Kanamori-Katayama, Artem S. Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto, Yuki I. Kawamura, Tsugumi Kawashima, Judith Kempfle, Tony Kenna, Juha Kere, Levon M. Khachigian, Toshio Kitamura, S. Peter Klinken, Alan J. Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew T. Kwon, Jeroen F. J. Laros, Weon-Ju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan Mackay‐Sim, R Manabe, Jessica C. Mar, Benoı̂t Marchand, Anthony Mathelier, Niklas Mejhert, Alison Meynert, Yosuke Mizuno, David Morais, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine L. Mummery, Mitsuyoshi Murata, Sayaka Nagao-Sato, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohmiya, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko Okada, Yasushi Okazaki, Valerio Orlando, Dmitry A. Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James Prendergast, Owen J. L. Rackham, Jordan A. Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten Beck Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi, Mizuho Sakai, Hiroki Sato, Hironori Satoh, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik Schultes, Gundula Schulze‐Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W. Shin, Christophe Simon, Daisuke Sugiyama, Takaaki Sugiyama, Masanori Suzuki, Naoko Suzuki, Rolf Swoboda, Peter A.C. ‘t Hoen, Michihira Tagami, Naoko Takahashi Tagami, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Zuotian Tatum, Mark Thompson, Hiroo Toyoda, Tetsuro Toyoda, Eivind Valen, Marc van de Wetering, Linda Berg, Roberto Verardo, Dipti Vijayan, Ilya E. Vorontsov, Wyeth W. Wasserman, Shoko Watanabe, Christine A. Wells, Louise N Winteringham, Ernst J. Wolvetang, Emily J. Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura, Shigehiro Yoshida, Susan E. Zabierowski, Peter Zhang, Xiaobei Zhao, S. Zucchelli, Kim Summers, Harukazu Suzuki, Carsten O. Daub, Jun Kawai, Peter Heutink, Yoshihide Hayashizaki, Tom C. Freeman, Boris Lenhard, Vladimir B. Bajić, Martin S. Taylor, Vsevolod J. Makeev, Albin Sandelin, David Hume, Piero Carninci, Yoshihide Hayashizaki,

Tópico(s)

RNA modifications and cancer

Resumo

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. A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types. FANTOM5 (standing for functional annotation of the mammalian genome 5) is the fifth major stage of a major international collaboration that aims to dissect the transcriptional regulatory networks that define every human cell type. Two Articles in this issue of Nature present some of the project's latest results. The first paper uses the FANTOM5 panel of tissue and primary cell samples to define an atlas of active, in vivo bidirectionally transcribed enhancers across the human body. These authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify more than 40,000 enhancer candidates from over 800 human cell and tissue samples. The enhancer atlas is used to compare regulatory programs between different cell types and identify disease-associated regulatory SNPs, and will be a resource for studies on cell-type-specific enhancers. In the second paper, single-molecule sequencing is used to map human and mouse transcription start sites and their usage in a panel of distinct human and mouse primary cells, cell lines and tissues to produce the most comprehensive mammalian gene expression atlas to date. The data provide a plethora of insights into open reading frames and promoters across different cell types in addition to valuable annotation of mammalian cell-type-specific transcriptomes.

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