Obesity-associated variants within FTO form long-range functional connections with IRX3

Scott Smemo, Juan J. Tena, Kyoung-Han Kim, Eric R. Gamazon, Noboru J. Sakabe, Carlos Gómez-Marín, Ivy Aneas, Flavia L. Credidio, Débora R. Sobreira, Nora F. Wasserman, Ju Hee Lee, Vijitha Puviindran, Davis Tam, Michael Shen, Joe Eun Son, Niki Alizadeh Vakili, Hoon-Ki Sung, Silvia Naranjo, Rafael D. Acemel, Miguel Manzanares, Andras Nagy, Nancy J. Cox, Chi-Chung Hui (), Jose Luis Gomez-Skarmeta () and Marcelo A. Nóbrega ()
Additional contact information
Scott Smemo: University of Chicago
Juan J. Tena: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain
Kyoung-Han Kim: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Eric R. Gamazon: Section of Genetic Medicine, University of Chicago
Noboru J. Sakabe: University of Chicago
Carlos Gómez-Marín: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain
Ivy Aneas: University of Chicago
Flavia L. Credidio: University of Chicago
Débora R. Sobreira: University of Chicago
Nora F. Wasserman: University of Chicago
Ju Hee Lee: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Vijitha Puviindran: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Davis Tam: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Michael Shen: University of Chicago
Joe Eun Son: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada
Niki Alizadeh Vakili: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Hoon-Ki Sung: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada
Silvia Naranjo: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain
Rafael D. Acemel: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain
Miguel Manzanares: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain
Andras Nagy: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada
Nancy J. Cox: University of Chicago
Chi-Chung Hui: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Jose Luis Gomez-Skarmeta: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain
Marcelo A. Nóbrega: University of Chicago

Nature, 2014, vol. 507, issue 7492, 371-375

Abstract: Obesity-associated noncoding sequences within FTO are functionally connected with IRX3, and long-range enhancers in this region recapitulate aspects of IRX3 expression, suggesting that the obesity-associated interval is part of IRX3 regulation; Irx3-deficient mice have lower body weight and are resistant to diet-induced obesity, suggesting IRX3 as a novel determinant of body mass and composition.

Date: 2014
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DOI: 10.1038/nature13138

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