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

Author

Listed:
  • 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
    Section of Genetic Medicine, 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)

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.

Suggested Citation

  • 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 P, 2014. "Obesity-associated variants within FTO form long-range functional connections with IRX3," Nature, Nature, vol. 507(7492), pages 371-375, March.
    • Handle: RePEc:nat:nature:v:507:y:2014:i:7492:d:10.1038_nature13138
    DOI: 10.1038/nature13138
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    Citations

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    Cited by:

    1. Moshe Shay Ben-Haim & Yishay Pinto & Sharon Moshitch-Moshkovitz & Vera Hershkovitz & Nitzan Kol & Tammy Diamant-Levi & Michal Schnaider Beeri & Ninette Amariglio & Haim Y. Cohen & Gideon Rechavi, 2021. "Dynamic regulation of N6,2′-O-dimethyladenosine (m6Am) in obesity," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Gerard Llimos & Vincent Gardeux & Ute Koch & Judith F. Kribelbauer & Antonina Hafner & Daniel Alpern & Joern Pezoldt & Maria Litovchenko & Julie Russeil & Riccardo Dainese & Riccardo Moia & Abdurraouf, 2022. "A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    3. Matthew C. Pahl & Claudia A. Doege & Kenyaita M. Hodge & Sheridan H. Littleton & Michelle E. Leonard & Sumei Lu & Rick Rausch & James A. Pippin & Maria Caterina Rosa & Alisha Basak & Jonathan P. Bradf, 2021. "Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Rita Dias Pereira & Pietro Biroli & Titus Galama & Stephanie von Hinke & Hans van Kippersluis & Cornelius A. Rietveld & Kevin Thom, 2022. "Gene-Environment Interplay in the Social Sciences," Papers 2203.02198, arXiv.org, revised Aug 2022.
    5. Ivy Aneas & Donna C. Decker & Chanie L. Howard & Débora R. Sobreira & Noboru J. Sakabe & Kelly M. Blaine & Michelle M. Stein & Cara L. Hrusch & Lindsey E. Montefiori & Juan Tena & Kevin M. Magnaye & S, 2021. "Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    6. Kashi Raj Bhattarai & Robert J. Mobley & Kelly R. Barnett & Daniel C. Ferguson & Baranda S. Hansen & Jonathan D. Diedrich & Brennan P. Bergeron & Satoshi Yoshimura & Wenjian Yang & Kristine R. Crews &, 2024. "Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Jin Woo Oh & Michael A. Beer, 2024. "Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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