The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase
Mansfield University · Churchill Hospital · +6 more institutions
Abstract
Variants in the FTO (fat mass and obesity associated) gene are associated with increased body mass index in humans. Here, we show by bioinformatics analysis that FTO shares sequence motifs with Fe(II)- and 2-oxoglutarate-dependent oxygenases. We find that recombinant murine Fto catalyzes the Fe(II)- and 2OG-dependent demethylation of 3-methylthymine in single-stranded DNA, with concomitant production of succinate, formaldehyde, and carbon dioxide. Consistent with a potential role in nucleic acid demethylation, Fto localizes to the nucleus in transfected cells. Studies of wild-type mice indicate that Fto messenger RNA (mRNA) is most abundant in the brain, particularly in hypothalamic nuclei governing energy…
Citation impact
- FWCI
- 36.46
- Percentile
- 100%
- References
- 29
Authors
25- TGThomas Gerken
Mansfield University, Churchill Hospital, University of Oxford, Wellcome/MRC Institute of Metabolic Science, Oxford Centre for Diabetes, Endocrinology and Metabolism, Science Oxford, Addenbrooke's Hospital, MRC Epidemiology Unit
- CAChristophe A. GirardCorresponding
Mansfield University, Churchill Hospital, University of Oxford, Wellcome/MRC Institute of Metabolic Science, Oxford Centre for Diabetes, Endocrinology and Metabolism, Science Oxford, Addenbrooke's Hospital, MRC Epidemiology Unit
- YLYi‐Chun Loraine TungCorresponding
Mansfield University, Churchill Hospital, University of Oxford, Wellcome/MRC Institute of Metabolic Science, Oxford Centre for Diabetes, Endocrinology and Metabolism, Science Oxford, Addenbrooke's Hospital, MRC Epidemiology Unit
- CJCelia J. WebbyCorresponding
Mansfield University, Churchill Hospital, University of Oxford, Wellcome/MRC Institute of Metabolic Science, Oxford Centre for Diabetes, Endocrinology and Metabolism, Science Oxford, Addenbrooke's Hospital, MRC Epidemiology Unit
- VSVladimı́r SaudekCorresponding
Mansfield University, Churchill Hospital, University of Oxford, Wellcome/MRC Institute of Metabolic Science, Oxford Centre for Diabetes, Endocrinology and Metabolism, Science Oxford, Addenbrooke's Hospital, MRC Epidemiology Unit
Topics & keywords
- Demethylation
- Nucleic acid
- FTO gene
- Chemistry
- Messenger RNA
- DNA demethylation
- RNA
- Biochemistry