Genome-wide analysis of promoter architecture in Drosophila melanogaster
- Roger A. Hoskins1,7,
- Jane M. Landolin1,7,
- James B. Brown2,7,
- Jeremy E. Sandler1,
- Hazuki Takahashi3,
- Timo Lassmann3,
- Charles Yu1,
- Benjamin W. Booth1,
- Dayu Zhang4,5,
- Kenneth H. Wan1,
- Li Yang6,
- Nathan Boley2,
- Justen Andrews4,
- Thomas C. Kaufman4,
- Brenton R. Graveley6,
- Peter J. Bickel2,
- Piero Carninci3,
- Joseph W. Carlson1 and
- Susan E. Celniker1,8
- 1 Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 97420, USA;
- 2 Department of Statistics, University of California, Berkeley, California 94720, USA;
- 3 Omics Science Center, RIKEN Yokohama Institute, Yokohama, 230-0045 Kanagawa, Japan;
- 4 Department of Biology, Indiana University, Bloomington, Indiana 47405, USA;
- 5 Center for Genomics and Bioinformatics, Indiana University, Bloomington, Indiana 47405, USA;
- 6 Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
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↵7 These authors contributed equally to this work.
Abstract
Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.
Footnotes
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↵8 Corresponding author.
E-mail celniker{at}fruitfly.org.
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[Supplemental material is available for this article. The sequencing data from this study have been submitted to the NCBI Sequence Read Archive (http://www.ncbi.nlm.nih.gov/Traces/sra/sra.cgi) under accession nos. SRX015329, SRA008141, and SRX015869.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.112466.110.
- Received July 2, 2010.
- Accepted October 20, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.
