Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE (original) (raw)
- Eivind Valen1,
- Giovanni Pascarella2,
- Alistair Chalk3,
- Norihiro Maeda4,
- Miki Kojima4,
- Chika Kawazu4,
- Mitsuyoshi Murata4,
- Hiromi Nishiyori4,
- Dejan Lazarevic2,8,
- Dario Motti2,
- Troels Torben Marstrand1,
- Man-Hung Eric Tang1,
- Xiaobei Zhao1,
- Anders Krogh1,
- Ole Winther1,
- Takahiro Arakawa4,
- Jun Kawai4,
- Christine Wells3,
- Carsten Daub5,
- Matthias Harbers7,
- Yoshihide Hayashizaki4,
- Stefano Gustincich2,
- Albin Sandelin1,9 and
- Piero Carninci4,6,9
- 1 The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes vej 5, DK-2200, Denmark;
- 2 The Giovanni Armenise-Harvard Foundation Laboratory, Sector of Neurobiology, International School for Advanced Studies (SISSA), Basovizza, 34012 Trieste, Italy;
- 3 The National Centre for Adult Stem Cell Research, The Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan QLD 4111, Australia;
- 4 LSA Technology Development Group, Omics Science Center, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045 Japan
- 5 LSA Bioinformatics Team, Omics Science Center, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045 Japan;
- 6 Functional Genomics Technology Team, Omics Science Center, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045 Japan;
- 7 DNAFORM Inc., Yokohama, Kanagawa 230-0046, Japan;
- 8 CBM Scrl–Consorzio per il Centro di Biomedicina Molecolare, Basovizza, 34012 Trieste, Italy
Abstract
Finding and characterizing mRNAs, their transcription start sites (TSS), and their associated promoters is a major focus in post-genome biology. Mammalian cells have at least 5–10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high-throughput sequencing of 5′ cDNA tags—DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth of novel core promoters that are preferentially used in hippocampus: This is the most comprehensive promoter data set for any tissue to date. Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.
Footnotes
↵9 Corresponding authors.
↵E-mail albin{at}binf.ku.dk; fax 45-3532-1281.
↵E-mail carninci{at}riken.jp; fax 81-48-4624868.[Supplemental material is available online at www.genome.org. CAGE tag sequences have been submitted to the DNA Data Bank of Japan (http://www.ddbj.nig.ac.jp/) under accession nos. AGAAA0000001–AGAAA0552486. Processed CAGE data sets are freely available at http://people.binf.ku.dk/albin/supplementary_data/hcamp/.]
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.084541.108.
- Received August 8, 2008.
- Accepted December 3, 2008.
Freely available online through the Genome Research Open Access option.
© 2009 American Meteorological Society