fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes模糊串联重复序列包含p53响应元素可以定义导致p53目标基因.pdfVIP

Fuzzy Tandem Repeats Containing p53 Response Elements May Define Species-Specific p53 Target Genes Iva Simeonova1,2,3, Vincent Lejour1,2,3, Boris Bardot1,2,3, Rachida Bouarich-Bourimi1,2,3, ´ 1,2,3, Ming Fang1,2,3, Laure Charbonnier1,2,3, Franck Toledo 1,2,3* Aurelie Morin 1 Institut Curie, Centre de Recherche, Paris, France, 2 UPMC Univ Paris 06, Paris, France, 3 CNRS UMR 3244, Paris, France 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. Citation: Simeonova I, Lejour V, Bardot B, Bouarich-Bourimi R, Morin A, et al. (2012) Fuzzy Tandem Repeats Containing p53 Response Elements May Define Species-Specific p53 Target Genes. PLoS Genet 8(6): e1002731. doi:10.1371/journal.pgen.1002731 Editor: Gregory S. Barsh, Stanford University School of Medicine, United States of America Received November 23, 2011; Accepted April 11, 2012; Published June 28, 2012 Copyright: 2012 Simeonova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted