The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate–Dependent Nucleic Acid Demethylase
Thomas Gerken,Christophe Girard,Yi-Chun Loraine Tung,Celia J. Webby,Vladimir Saudek,Kirsty S. Hewitson,Giles S.H. Yeo,Michael A. McDonough,Sharon Cunliffe,Luke A. McNeill,Juris Galvanovskis,Patrik Rorsman,Peter Robins,Xavier Prieur,Anthony P. Coll,Marcella Ma,Zorica Jovanovic,I. Sadaf Farooqi,Barbara Sedgwick,Inês Barroso,Tomas Lindahl,Chris P. Ponting,Frances M. Ashcroft,Stephen O'Rahilly,Christopher J. Schofield +24 more
TLDR
It is found 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.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.read more
Citations
More filters
疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
“Bioinformatics” 특집을 내면서
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Journal ArticleDOI
Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
Kate D. Meyer,Yogesh Saletore,Paul Zumbo,Olivier Elemento,Christopher E. Mason,Samie R. Jaffrey +5 more
TL;DR: A method is presented for transcriptome-wide m(6)A localization, which combines m( 6)A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq) and reveals insights into the epigenetic regulation of the mammalian transcriptome.
Journal ArticleDOI
N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.
Guifang Jia,Ye Fu,Xu Zhao,Xu Zhao,Qing Dai,Guanqun Zheng,Ying Yang,Ying Yang,Chengqi Yi,Tomas Lindahl,Tao Pan,Yun-Gui Yang,Yun-Gui Yang,Chuan He +13 more
TL;DR: FTO exhibits efficient oxidative demethylation activity of abundant N6-methyladenosine (m6A) residues in RNA in vitro, and it is shown that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.
Journal ArticleDOI
Five years of GWAS discovery
Peter M. Visscher,Peter M. Visscher,Matthew A. Brown,Mark I. McCarthy,Mark I. McCarthy,Jian Yang +5 more
TL;DR: The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs), which were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders.
References
More filters
疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Book
The Mouse Brain in Stereotaxic Coordinates
TL;DR: The 3rd edition of this atlas is now in more practical 14"x11" format for convenient lab use and includes a CD of all plates and diagrams, as well as Adobe Illustrator files of the diagrams, and a variety of additional useful material.
Journal ArticleDOI
Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
“Bioinformatics” 특집을 내면서
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Journal ArticleDOI
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
Related Papers (5)
A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity
Timothy M. Frayling,Nicholas J. Timpson,Michael N. Weedon,Eleftheria Zeggini,Eleftheria Zeggini,Eleftheria Zeggini,Rachel M. Freathy,Cecilia M. Lindgren,John R. B. Perry,Katherine S. Elliott,Katherine S. Elliott,Hana Lango,Nigel W. Rayner,Nigel W. Rayner,Nigel W. Rayner,Beverley M. Shields,Lorna W. Harries,Jeffrey C. Barrett,Jeffrey C. Barrett,Sian Ellard,Christopher J. Groves,Christopher J. Groves,Bridget A. Knight,Ann-Marie Patch,Andy R Ness,Shah Ebrahim,Debbie A Lawlor,Susan M. Ring,Yoav Ben-Shlomo,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Ulla Sovio,Ulla Sovio,Amanda J. Bennett,Amanda J. Bennett,David Melzer,Luigi Ferrucci,Ruth J. F. Loos,Inês Barroso,Nicholas J. Wareham,Fredrik Karpe,Fredrik Karpe,Katharine R. Owen,Katharine R. Owen,Lon R. Cardon,Mark Walker,Graham A. Hitman,Graham A. Hitman,Colin N. A. Palmer,Colin N. A. Palmer,Alex S. F. Doney,Alex S. F. Doney,Andrew D. Morris,George Davey Smith,Andrew T. Hattersley,Mark I. McCarthy +55 more
Variation in FTO contributes to childhood obesity and severe adult obesity
Christian Dina,David Meyre,Sophie Gallina,Emmanuelle Durand,Antje Körner,Peter Jacobson,Lena M. S. Carlsson,Wieland Kiess,Vincent Vatin,Cécile Lecoeur,Jérôme Delplanque,Emmanuel Vaillant,François Pattou,Juan Ruiz,Jacques Weill,Claire Levy-Marchal,Fritz F. Horber,Natascha Potoczna,Serge Hercberg,Catherine Le Stunff,Pierre Bougnères,Peter Kovacs,Michel Marre,Beverley Balkau,Beverley Balkau,Stéphane Cauchi,Jean-Claude Chèvre,Philippe Froguel,Philippe Froguel +28 more
Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.
Angelo Scuteri,Serena Sanna,Wei-Min Chen,Manuela Uda,Giuseppe Albai,James B. Strait,Samer S. Najjar,Ramaiah Nagaraja,Marco Orru,Gianluca Usala,Mariano Dei,Sandra Lai,Andrea Maschio,Fabio Busonero,Antonella Mulas,Georg Ehret,Ashley A Fink,Alan B. Weder,Richard S. Cooper,Pilar Galan,Aravinda Chakravarti,David Schlessinger,Antonio Cao,Edward G. Lakatta,Gonçalo R. Abecasis +24 more