Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes

Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retin...

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Veröffentlicht in:PLoS genetics 2012-06, Vol.8 (6), p.e1002731-e1002731
Hauptverfasser: Simeonova, Iva, Lejour, Vincent, Bardot, Boris, Bouarich-Bourimi, Rachida, Morin, Aurélie, Fang, Ming, Charbonnier, Laure, Toledo, Franck
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container_title PLoS genetics
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creator Simeonova, Iva
Lejour, Vincent
Bardot, Boris
Bouarich-Bourimi, Rachida
Morin, Aurélie
Fang, Ming
Charbonnier, Laure
Toledo, Franck
description Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (Rbl2) gene to produce p130 in murine, but not human, cells. We found intronic fuzzy tandem repeats containing perfect p53 response elements to be important for this regulation. We next identified two other murine genes regulated by p53 via fuzzy tandem repeats: Ncoa1 and Klhl26. The repeats are poorly conserved in evolution, and the p53-dependent regulation of the murine genes is lost in humans. Our results indicate a role for the rapid evolution of tandem repeats in shaping differences in p53 regulatory networks between mammalian species.
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subjects Animals
Biology
Cells, Cultured
Evolution, Molecular
Evolutionary genetics
Fibroblasts - cytology
Fibroblasts - metabolism
Fuzzy algorithms
Fuzzy logic
Fuzzy systems
Gene expression
Gene Expression Regulation
Genes
Genetics
Humans
Introns - genetics
Life Sciences
Mice
Mutation
Nuclear Receptor Coactivator 1 - genetics
Nuclear Receptor Coactivator 1 - metabolism
Physiological aspects
Proteins
Response Elements - genetics
Retinoblastoma - genetics
Retinoblastoma-Like Protein p130 - genetics
Retinoblastoma-Like Protein p130 - metabolism
Rodents
Species Specificity
Tandem Repeat Sequences - genetics
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
title Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes
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