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

First Author  Simeonova I Year  2012
Journal  PLoS Genet Volume  8
Issue  6 Pages  e1002731
PubMed ID  22761580 Mgi Jnum  J:187174
Mgi Id  MGI:5435635 Doi  10.1371/journal.pgen.1002731
Citation  Simeonova I, et al. (2012) Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes. PLoS Genet 8(6):e1002731
abstractText  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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