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Nature Genetics - 38, 626 - 635 (2006)
Published online: 28 April 2006; Corrected online: 05 May 2006; Corrected online: 29 August 2007 | doi:10.1038/ng1789

There is a Corrigendum (September 2007) associated with this Article.

Genome-wide analysis of mammalian promoter architecture and evolution

Piero Carninci1, 2, 21, Albin Sandelin1, 3, 21, Boris Lenhard1, 3, 20, 21, Shintaro Katayama1, Kazuro Shimokawa1, Jasmina Ponjavic1, 20, Colin A M Semple1, 4, Martin S Taylor1, 5, Pär G Engström3, Martin C Frith1, 6, Alistair R R Forrest6, Wynand B Alkema3, Sin Lam Tan7, Charles Plessy2, Rimantas Kodzius1, 2, Timothy Ravasi1, 6, 8, Takeya Kasukawa1, 9, Shiro Fukuda1, Mutsumi Kanamori-Katayama1, Yayoi Kitazume1, Hideya Kawaji1, 9, Chikatoshi Kai1, Mari Nakamura1, Hideaki Konno1, Kenji Nakano1, 9, Salim Mottagui-Tabar3, 20, Peter Arner10, Alessandra Chesi11, Stefano Gustincich11, Francesca Persichetti12, Harukazu Suzuki1, Sean M Grimmond6, Christine A Wells19, Valerio Orlando13, Claes Wahlestedt3, 20, Edison T Liu14, Matthias Harbers15, Jun Kawai1, 2, Vladimir B Bajic1, 7, 16, David A Hume1, 6, 21 & Yoshihide Hayashizaki1, 2, 17, 18

1  Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.

2  Genome Science Laboratory, Discovery Research Institute, RIKEN Wako Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.

3  Center for Genomics and Bioinformatics, Karolinska Institutet, Berzelius v. 35, S-171 77 Stockholm, Sweden.

4  UK Medical Research Council (MRC) Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.

5  University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.

6  Australian Research Council (ARC) Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane Qld, 4072, Australia.

7  Knowledge Extraction Laboratory, Institute for Infocomm Research, 21 Heng Mui Keng Terrace, 119613, Singapore.

8  Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, 0412 La Jolla, California 92093, USA.

9  Broadband Communication Service Business Unit, Network Service Solution Business Group, NTT Software Corporation, Teisan Kannai Bldg. 209, Yamashita-cho Naka-ku, Yokohama, Kanagawa, 231-8551, Japan.

10  Department of Medicine, Karolinska Institute, Huddinge University Hospital, S 141 86 Huddinge, Sweden.

11  The Giovanni Armenise–Harvard Foundation Laboratory, Sector of Neurobiology, International School for Advanced Studies-Scuola Internazionale Superiore Studi Avanzati (I.S.A.S.-S.I.S.S.A.), AREA Science Park, Padriciano 99, 34012 Trieste, Italy.

12  Sector of Neurobiology, I.S.A.S.-S.I.S.S.A., AREA Science Park, Padriciano 99, 34012 Trieste, Italy.

13  Dulbecco Telethon Institute, Institute of Genetics and Biophysics, Consiglio Nazionale delle Ricerche (IGB CNR), Epigenetics and Genome Reprogramming Laboratory, Pietro Castellino Street 111, Napoli, 80131, Italy.

14  Genome Institute of Singapore, 60 Biopolis Street #02-01, Singapore 138672.

15  Kabushiki Kaisha Dnaform, 1-3-35, Mita, Minato-ku, Tokyo, 108-0073, Japan.

16  South African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville, South Africa.

17  Yokohama City University, 1-7-29 Suehiro-cho Tsurumi-ku Yokohama 230-0045 Japan.

18  Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi Ibaraki-ken, 305-8577, Japan.

19  The Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan Campus, Kessels Road, Queensland 4111, Australia.

20  Present addresses: Bergen Center for Computational Science, Unifob AS, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway (B.L.), Scripps Florida, Jupiter, Florida 33458, USA (C.W.), Department of Molecular Medicine, National Public Health Instititute, Department of Medical Genetics, University of Helsinki, Biomedicum, FIN-00251 Helsinki, Finland (S.M.-T.) and MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK (J.P.).

21  These authors contributed equally to this work.

Correspondence should be addressed to David A Hume or Yoshihide Hayashizaki

Mammalian promoters can be separated into two classes, conserved TATA box–enriched promoters, which initiate at a well-defined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3' UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them.

NOTE: In the version of this article initially published online, the x-axis of Figure 4b was mislabeled. Specifically, the five groups on the x-axis should be labeled:
No mutation
PyPu to PuPu
PyPu to PuPy
PyPu to PyPu
PyPu to PyPy
The error has been corrected for all versions of the article.

NOTE: In the version of this article initially published, two of the smaller bar plots in Figure 1e were mistakenly duplicated. Specifically, the Zfp385 plot is an erroneous copy of the 137774 plot, and the Txndc7 plot is an erroneous copy of the Pik3r5 plot. See below for the corrected version of the figure. This error does not change the conclusions of the study in any way, as the bar plots are just a few visual examples of more than 5,000 tag clusters, and the correct plots follow the same distribution patterns as the erroneous ones. This error has been corrected in the HTML and PDF versions of the article.


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EISSN: 1546-1718
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