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

Nepal, C., Hadzhiev, Y., Previty, C., Haberle, V., Li, N., Takahashi, H., Suzuki, A.M., Sheng, Y., Abdelhamid, R., Anand, S., Gehrig, J., Akalin, A., Kockx, C., van der Sloot, A., van Ijcken, W., Armant, O., Rastegar, S., Straehle, U., Stupka, E., Carninci, P., Lenhard, B., and Muller, F.
Genome research   23(11): 1938-50 (Journal)
Registered Authors
Armant, Olivier, Gehrig, Jochen, Hadzhiev, Yavor, Li, Nan, Müller, Ferenc, Rastegar, Sepand, Strähle, Uwe
MeSH Terms
  • Animals
  • Embryonic Development/genetics*
  • Evolution, Molecular
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Genes
  • Genome
  • Phylogeny
  • Promoter Regions, Genetic
  • Purines/metabolism*
  • RNA/genetics
  • RNA/metabolism
  • RNA Caps/genetics
  • RNA Splicing
  • Transcription Initiation Site*
  • Transcriptome
  • Vertebrates/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics*
24002785 Full text @ Genome Res.

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 datasets 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 specialised 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.

Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes