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

PLoS Genet. 2012 Jun;8(6):e1002731. doi: 10.1371/journal.pgen.1002731. Epub 2012 Jun 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Evolution, Molecular
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation*
  • Humans
  • Introns / genetics
  • Mice
  • Mutation
  • Nuclear Receptor Coactivator 1 / genetics
  • Nuclear Receptor Coactivator 1 / metabolism
  • Response Elements / genetics
  • Retinoblastoma / genetics*
  • Retinoblastoma-Like Protein p130* / genetics
  • Retinoblastoma-Like Protein p130* / metabolism
  • Species Specificity
  • Tandem Repeat Sequences / genetics*
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism


  • Rbl2 protein, mouse
  • Retinoblastoma-Like Protein p130
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1