Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis

Chirag Nepal, Yavor Hadzhiev, Christopher Previti, Vanja Haberle, Nan Li, Hazuki Takahashi, Ana Maria M Suzuki, Ying Sheng, Rehab F. Abdelhamid, Santosh Anand, Jochen Gehrig, Altuna Akalin, Christel E M Kockx, Antoine A J Van Der Sloot, Wilfred F J Van IJcken, Olivier Armant, Sepand Rastegar, Craig Watson, Uwe Strahle, Elia StupkaPiero Carninci, Boris Lenhard, Ferenc Muller

Research output: Contribution to journalArticlepeer-review


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 intronicRNA(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.

Original languageEnglish
Pages (from-to)1938-1950
Number of pages13
JournalGenome Research
Issue number11
Publication statusPublished - Nov 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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