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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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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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.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1002731</identifier><identifier>PMID: 22761580</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PLoS genetics, 2012-06, Vol.8 (6), p.e1002731-e1002731</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Simeonova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: 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. 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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.</description><subject>Animals</subject><subject>Biology</subject><subject>Cells, Cultured</subject><subject>Evolution, Molecular</subject><subject>Evolutionary genetics</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Fuzzy algorithms</subject><subject>Fuzzy logic</subject><subject>Fuzzy systems</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetics</subject><subject>Humans</subject><subject>Introns - genetics</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mutation</subject><subject>Nuclear Receptor Coactivator 1 - genetics</subject><subject>Nuclear Receptor Coactivator 1 - metabolism</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Response Elements - genetics</subject><subject>Retinoblastoma - genetics</subject><subject>Retinoblastoma-Like Protein p130 - genetics</subject><subject>Retinoblastoma-Like Protein p130 - metabolism</subject><subject>Rodents</subject><subject>Species Specificity</subject><subject>Tandem Repeat Sequences - genetics</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk11v0zAUhiMEYmPwDxBEQkJw0WLHcZ3cIFUTY5UqJvF1a9nOceoqsbPYmeh-PW6bjXbiAq5sHT_n9TmvfZLkJUZTTBj-sHZDb0Uz7WqwU4xQxgh-lJxiSsmE5Sh_fLA_SZ55v0aI0KJkT5OTLGMzTAt0msiL4fZ2kwZhK2jTHjoQwafK2SCMNbZOO0pi2HfOekihgRZsBFqxSSvQxkLqO1AG_GS3aqN2GUH0NYQ0lgb-efJEi8bDi3E9S35cfPp-fjlZXn1enM-XE8UyHCZ4pllFhZAVZYKUJKs0qkCWM8lKJoUuSUGxJJWWQrEig0LNCC0Z1bFBGZsnZ8nrvW7XOM9HezzHBMe2Ec2KSCz2ROXEmne9aUW_4U4Yvgu4vuaiD0Y1wHFVaK2JoqSQeUWJyDHOMZQgKSOgVdT6ON42yBYqFW3pRXMkenxizYrX7oYTUkTvZ1Hg_V5g9SDtcr7k2xjKGWZ5Vt7gyL4bL-vd9QA-8NZ4BU0jLLgh9oiyHJUF3rnw5gH6dydGqhaxWWO1izWqrSifE5QTxAqC_5Q4UttvAb9CLQbv-eLb1_9gv_w7e_XzmH17wK5ANGHlXTMEE3_kMZjvQdU773vQ96ZixLcTc2cE304MHycmpr06fMf7pLsRIb8B9S8PZQ</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Simeonova, Iva</creator><creator>Lejour, Vincent</creator><creator>Bardot, Boris</creator><creator>Bouarich-Bourimi, Rachida</creator><creator>Morin, Aurélie</creator><creator>Fang, Ming</creator><creator>Charbonnier, Laure</creator><creator>Toledo, Franck</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4976-9593</orcidid></search><sort><creationdate>20120601</creationdate><title>Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes</title><author>Simeonova, Iva ; Lejour, Vincent ; Bardot, Boris ; Bouarich-Bourimi, Rachida ; Morin, Aurélie ; Fang, Ming ; Charbonnier, Laure ; Toledo, Franck</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c721t-16f7d5aabd57a3932df0deb96b797baf93851b3dfbac782e8c635975f740b2733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Biology</topic><topic>Cells, Cultured</topic><topic>Evolution, Molecular</topic><topic>Evolutionary genetics</topic><topic>Fibroblasts - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22761580</pmid><doi>10.1371/journal.pgen.1002731</doi><orcidid>https://orcid.org/0000-0003-4976-9593</orcidid><oa>free_for_read</oa></addata></record> |
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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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