The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.
نویسندگان
چکیده
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.
منابع مشابه
Molecular Medicine Select
Recently, genome-wide association studies have linked variations in alleles of the FTO (fat mass and obesity associated) gene to obesity. Gerken et al. (2007) now reveal that FTO encodes a nucleic acid demethylase. Upon examination of the sequence of FTO, the authors noticed a domain that had homology to 2-oxoglutarate oxygenases. These enzymes are involved in a variety of processes including D...
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Genomewide-association studies have revealed that SNPs (single nucleotide polymorphisms) in FTO (fat mass and obesity-associated) are robustly associated with BMI (body mass index) and obesity. FTO is an Fe(II) 2-OG (2-oxoglutarate)-dependent dioxygenase that can demethylate 3-meT (3-methylthymine) in single-stranded DNA, as well as 3-meU (3-methyluracil) and N6-methyl adenosine in RNA. In the ...
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ورودعنوان ژورنال:
- Science
دوره 318 5855 شماره
صفحات -
تاریخ انتشار 2007