Abstract:
: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.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Simeonova I,Lejour V,Bardot B,Bouarich-Bourimi R,Morin A,Fang M,Charbonnier L,Toledo Fdoi
10.1371/journal.pgen.1002731subject
Has Abstractpub_date
2012-06-01 00:00:00pages
e1002731issue
6eissn
1553-7390issn
1553-7404pii
PGENETICS-D-11-02542journal_volume
8pub_type
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