Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis
- Chirag Nepal1,2,12,
- Yavor Hadzhiev3,12,
- Christopher Previti1,2,12,14,
- Vanja Haberle1,2,
- Nan Li3,
- Hazuki Takahashi4,
- Ana Maria M. Suzuki4,12,
- Ying Sheng1,2,
- Rehab F. Abdelhamid4,
- Santosh Anand5,
- Jochen Gehrig3,13,
- Altuna Akalin1,2,15,
- Christel E.M. Kockx6,
- Antoine A.J. van der Sloot6,
- Wilfred F.J. van IJcken6,
- Olivier Armant7,
- Sepand Rastegar7,
- Craig Watson8,
- Uwe Strähle7,
- Elia Stupka5,9,
- Piero Carninci4,16,
- Boris Lenhard1,2,10,11,16 and
- Ferenc Müller3,16
- 1Department of Biology, University of Bergen, Bergen N-5008, Norway;
- 2Computational Biology Unit, Uni BCCS, Bergen N-5008, Norway;
- 3School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston B15 2TT, United Kingdom;
- 4RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama 230-0045, Japan;
- 5Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom;
- 6Dutch Center for Biomics, Erasmus MC, Rotterdam 3015 GE, Netherlands;
- 7Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen 76344, Germany;
- 8Tropical Aquaculture Laboratory, Program in Fisheries and Aquatic Sciences, School of Forest Resources and Conservation, Institute of Food and Agricultural Sciences, University of Florida, Ruskin, Florida 33570, USA;
- 9Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan 20132, Italy;
- 10Imperial College and MRC Clinical Sciences Centre, London, Faculty of Medicine, Hammersmith Hospital Campus, London W12 0NN, United Kingdom;
- 11Department of Informatics, University of Bergen, Bergen N-5008, Norway
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↵12 These authors contributed equally to this paper.
Abstract
Spatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we provide a first and comprehensive description of the core promoter repertoire and its dynamic use during the development of a vertebrate embryo. By using cap analysis of gene expression (CAGE), we mapped transcription initiation events at single nucleotide resolution across 12 stages of zebrafish development. These CAGE-based transcriptome maps reveal genome-wide rules of core promoter usage, structure, and dynamics, key to understanding the control of gene regulation during vertebrate ontogeny. They revealed the existence of multiple classes of pervasive intra- and intergenic post-transcriptionally processed RNA products and their developmental dynamics. Among these RNAs, we report splice donor site-associated intronic RNA (sRNA) to be specific to genes of the splicing machinery. For the identification of conserved features, we compared the zebrafish data sets to the first CAGE promoter map of Tetraodon and the existing human CAGE data. We show that a number of features, such as promoter type, newly discovered promoter properties such as a specialized purine-rich initiator motif, as well as sRNAs and the genes in which they are detected, are conserved in mammalian and Tetraodon CAGE-defined promoter maps. The zebrafish developmental promoterome represents a powerful resource for studying developmental gene regulation and revealing promoter features shared across vertebrates.
Footnotes
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↵14 German Cancer Research Center (DKFZ), Genomics & Proteomics Core Facility (GPCF), Im Neuenheimer Feld 580/TP3, Heidelberg 69120, Germany;
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↵15 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
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↵16 Corresponding authors
E-mail carninci{at}riken.jp
E-mail b.lenhard{at}imperial.ac.uk
E-mail f.mueller{at}bham.ac.uk
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[Supplemental material is available for this article.]
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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.153692.112.
- Received December 15, 2012.
- Accepted August 8, 2013.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
