title: Identification of p53-target genes in Danio rerio.
abstract: 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.
authors: Medical Genetics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, 71013, Italy.|PhD Program, Molecular Genetics applied to Medical Sciences, University of Brescia, Brescia, 25123, Italy.
authors: Barbara
authors: B
authors: Mandriani
authors: Bioinformatics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
authors: Stefano
authors: S
authors: Castellana
authors: Medical Genetics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, 71013, Italy.
authors: Carmela
authors: C
authors: Rinaldi
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Marta
authors: M
authors: Manzoni
authors: Medical Genetics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, 71013, Italy.
authors: Santina
authors: S
authors: Venuto
authors: Instituto de Neurociencias CSIC-UMH, Av. Ramon y Cajal s/n 03550 Sant Joan d'Alacant, Spain.
authors: Eva
authors: E
authors: Rodriguez-Aznar
authors: Instituto de Neurociencias CSIC-UMH, Av. Ramon y Cajal s/n 03550 Sant Joan d'Alacant, Spain.
authors: Juan
authors: J
authors: Galceran
authors: Instituto de Neurociencias CSIC-UMH, Av. Ramon y Cajal s/n 03550 Sant Joan d'Alacant, Spain.
authors: M Angela
authors: MA
authors: Nieto
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Giuseppe
authors: G
authors: Borsani
authors: Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
authors: Eugenio
authors: E
authors: Monti
authors: Bioinformatics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
authors: Tommaso
authors: T
authors: Mazza
authors: Medical Genetics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, 71013, Italy.
authors: Giuseppe
authors: G
authors: Merla
authors: Medical Genetics Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, 71013, Italy.
authors: Lucia
authors: L
authors: Micale
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D016678:Genome; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D016415:Sequence Alignment; D015398:Signal Transduction; D053449:TNF Receptor-Associated Factor 4 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D060466:Axin Protein; C000601280:Axin1 protein, zebrafish; D002135:Calcium-Binding Proteins; D024141:Collagen Type IV; D050676:Core Binding Factor Alpha 2 Subunit; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D053449:TNF Receptor-Associated Factor 4; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C494374:hspa8 protein, zebrafish; C472526:runx1 protein, zebrafish