Identification of p53-target genes in Danio rerio

Mandriani, B., Castellana, S., Rinaldi, C., Manzoni, M., Venuto, S., Rodriguez-Aznar, E., Galceran, J., Nieto, M.A., Borsani, G., Monti, E., Mazza, T., Merla, G., Micale, L.
Scientific Reports   6: 32474 (Journal)
Registered Authors
Borsani, Giuseppe, Galceran, Juan, Nieto, Angela, Nieto-López, Francisco
Gene regulation, Genetics
MeSH Terms
  • Animals
  • Axin Protein/genetics
  • Axin Protein/metabolism
  • Base Sequence
  • Binding Sites
  • Calcium-Binding Proteins/genetics
  • Calcium-Binding Proteins/metabolism
  • Collagen Type IV/genetics
  • Collagen Type IV/metabolism
  • Core Binding Factor Alpha 2 Subunit/genetics
  • Core Binding Factor Alpha 2 Subunit/metabolism
  • Evolution, Molecular
  • Gene Expression Regulation
  • Genome*
  • HSC70 Heat-Shock Proteins/genetics
  • HSC70 Heat-Shock Proteins/metabolism
  • HSP40 Heat-Shock Proteins/genetics
  • HSP40 Heat-Shock Proteins/metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Response Elements*
  • Sequence Alignment
  • Signal Transduction
  • TNF Receptor-Associated Factor 4/genetics
  • TNF Receptor-Associated Factor 4/metabolism
  • Transcription, Genetic*
  • Tumor Suppressor Protein p53/genetics*
  • Tumor Suppressor Protein p53/metabolism
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
27581768 Full text @ Sci. Rep.
To orchestrate the genomic response to cellular stress signals, p53 recognizes and binds to DNA containing specific and well-characterized p53-responsive elements (REs). Differences in RE sequences can strongly affect the p53 transactivation capacity and occur even between closely related species. Therefore, the identification and characterization of a species-specific p53 Binding sistes (BS) consensus sequence and of the associated target genes may help to provide new insights into the evolution of the p53 regulatory networks across different species. Although p53 functions were studied in a wide range of species, little is known about the p53-mediated transcriptional signature in Danio rerio. Here, we designed and biochemically validated a computational approach to identify novel p53 target genes in Danio rerio genome. Screening all the Danio rerio genome by pattern-matching-based analysis, we found p53 RE-like patterns proximal to 979 annotated Danio rerio genes. Prioritization analysis identified a subset of 134 candidate pattern-related genes, 31 of which have been investigated in further biochemical assays. Our study identified runx1, axin1, traf4a, hspa8, col4a5, necab2, and dnajc9 genes as novel direct p53 targets and 12 additional p53-controlled genes in Danio rerio genome. The proposed combinatorial approach resulted to be highly sensitive and robust for identifying new p53 target genes also in additional animal species.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes