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

ABSTRACT: Genome-wide association studies in diverse populations have reproducibly associated variants within introns of FTO with increased risk for obesity and type-2 diabetes.While the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that FTO expression levels influence body mass and composition phenotypes. Yet, no direct connection between the obesity-associated intronic variants and FTO expression or function has been made. We show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, primarily with the homeobox gene IRX3, rather than with FTO.

ORGANISM(S): Mus musculus Danio rerio

PROVIDER: GSE52830 | GEO | 2014/02/24

SECONDARY ACCESSION(S): PRJNA230260

REPOSITORIES: GEO

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

Project description:Genome-wide association studies in diverse populations have reproducibly associated variants within introns of FTO with increased risk for obesity and type-2 diabetes.While the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that FTO expression levels influence body mass and composition phenotypes. Yet, no direct connection between the obesity-associated intronic variants and FTO expression or function has been made. We show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, primarily with the homeobox gene IRX3, rather than with FTO. 4C-seq samples for Fto/fto and Irx3/irx3a genes promoters in different samples: adult mouse brain, E9.5 mouse embryos and 24hpf zebrafish embryos.

2014-02-24 | E-GEOD-52830 | biostudies-arrayexpress

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

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

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Circular chromatin conformation capture (4C-seq) experiments for viewpoints on the promoters of Rpgrip1l/Fto, Irx3, Irx5 and Irx6 in mouse hypothalamus

Project description:We performed 4C to analyze long-range interactions between the promoters of Rpgrip1l/Fto, Irx3, Irx5 and Irx6 and a region in the first intron of the FTO gene that has been associated with obesity. 3 whole mouse hypothalami were used to obtain the data.

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Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia [UMI4C]

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Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia [HiChIP]

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Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia [ATAC-Seq]

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Genome wide analysis reveals association of a FTO gene variant with epigenetic changes of several genes in human blood

Project description:FTO gene variants show the strongest association to obesity so far, but the role of the gene in obesity remains unclear. The FTO protein is a demethylation enzyme, which suggests that the link to obesity could be mediated through epigenetic changes. Herein, we determine the genome wide DNA methylation profile in blood from 47 female preadolescents and detect changes in five methylated regions, corresponding to six genes, associated with the FTO risk allele (rs9939609). In addition, we identify 20 differentially methylated regions associated with obesity. Our findings indicate that the effect of the FTO obesity risk allele may be mediated through epigenetic changes. Further, the identified regions might prove valuable biomarkers for the diagnosis and prognosis of obesity and comorbidites, such as cardiovascular disease. Bisulphite converted DNA from 47 girls were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. Half of the subjects are carriers of the FTO obesity risk allele (AA) and half of the normal allele (TT). In addition, both obese and normal-weigh indiviudals were included.

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Adiponectin-cre FTO flox/flox and FTO flox/flox mouse white fat tissues

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Adiponectin-cre FTO flox/flox and FTO flox/flox mouse white fat tissues

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