The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase

Gerken, Thomas, Girard, Christophe A., Tung, Yi-Chun Loraine, Webby, Celia J., Saudek, Vladimir, Hewitson, Kirsty S., Yeo, Giles S. H., McDonough, Michael A., Cunliffe, Sharon, McNeill, Luke A., Galvanovskis, Juris, Rorsman, Patrik, Robins, Peter, Prieur, Xavier, Coll, Anthony P., Ma, Marcella, Jovanovic, Zorica, Farooqi, I. Sadaf, Sedgwick, Barbara, Barroso, Ines, Lindahl, Tomas, Ponting, Chris P., Ashcroft, Frances M., O’Rahilly, Stephen and Schofield, Christopher J. (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science, 318 5855: 1469-1472. doi:10.1126/science.1151710


Author Gerken, Thomas
Girard, Christophe A.
Tung, Yi-Chun Loraine
Webby, Celia J.
Saudek, Vladimir
Hewitson, Kirsty S.
Yeo, Giles S. H.
McDonough, Michael A.
Cunliffe, Sharon
McNeill, Luke A.
Galvanovskis, Juris
Rorsman, Patrik
Robins, Peter
Prieur, Xavier
Coll, Anthony P.
Ma, Marcella
Jovanovic, Zorica
Farooqi, I. Sadaf
Sedgwick, Barbara
Barroso, Ines
Lindahl, Tomas
Ponting, Chris P.
Ashcroft, Frances M.
O’Rahilly, Stephen
Schofield, Christopher J.
Title The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase
Formatted title
The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase
Journal name Science   Check publisher's open access policy
ISSN 0036-8075
1095-9203
Publication date 2007-11-30
Sub-type Article (original research)
DOI 10.1126/science.1151710
Open Access Status Not yet assessed
Volume 318
Issue 5855
Start page 1469
End page 1472
Total pages 4
Place of publication Washington, DC, United States
Publisher American Association for the Advancement of Science
Language eng
Formatted 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 balance, and that Fto mRNA levels in the arcuate nucleus are regulated by feeding and fasting. Studies can now be directed toward determining the physiologically relevant FTO substrate and how nucleic acid methylation status is linked to increased fat mass.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
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Citation counts: TR Web of Science Citation Count  Cited 748 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 30 Oct 2011, 20:14:34 EST by Celia Webby on behalf of Faculty Of Health Sciences