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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

| PRJNA230260 | ENA

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.

2021-03-20 | E-MTAB-10195 | biostudies-arrayexpress

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.

2012-01-10 | E-GEOD-27860 | biostudies-arrayexpress

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

Project description:Single nucleotide polymorphisms in intron 1 of the fat mass and obesity-associated (FTO) gene were found to be associated with an increased risk of adult obesity. Enhanced FTO expression in mice leads to hyperphagia, increased fat mass, and higher body weight. Neuronal-specific FTOâ??deleted mice have an identical lean body weight phenotype to global FTO-deleted mice. The physiological role of adipose FTO in the homeostasis of energy regulation remains to be elucidated. We used microarrays to elucidate the metabolic pathways that are regulated by FTO in the white fat. FTO flox/flox and Adiponectin-cre FTO flox/flox (AFO) mice were fed with chow diet. White fat tissues from epididymal adipose pad were harvested under ad lib condition for RNA isolation. Three independent pools of FTO flox/flox and AFO mouse white fat RNA were included in the study.

2016-07-03 | E-GEOD-65098 | biostudies-arrayexpress

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

2016-01-01 | GSE65098 | GEO

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

2012-01-10 | GSE27860 | GEO

Next Generation Sequencing of BMDM overexpressing GFP, IRX3-WT, IRX3-S361A and IRX3-S389A

Project description:IRX3 is a transcriptional factor, which play important functions in developmental processes. But the role of IRX3 in immune cells are less studied. So we sequenced mRNA from BMDMs overexpressing GFP, IRX3, as well as two phosphorylation site mutants-S361A and S389A respectively, to address the roles of IRX3 in macrophages.

2021-07-29 | GSE178574 | GEO

Gene expression analysis of the effect of Irx3 knockout in mouse hypothalamus compared with wild-type (in high-fat diet)

Project description:To establish the roles of Irx3 in molecular and physiological brain phenotypes associated with obesity, we performed transcriptomic analysis (RNA-seq) on hypothalami from Irx3 CRISPR/Cas9 knockout mice and wild-type littermates.

2021-03-14 | E-MTAB-10186 | biostudies-arrayexpress

Quantitative Proteomics of Mouse Liver (FTO-KO,WT) in response to DEN injection

Project description:Single nucleotide polymorphisms in the FTO gene encoding a m6A demthylase are associated with obesity and cancer development. However, the functional role of FTO in the developemnt of progression of hepatocellular carcinoma (HCC) as a proteotypic obesity-associated cancer remains unclear. Here, we have generated mice with hepatic FTO deficiency (FTOL-KO) and subjected them to DEN induced HCC-development. FTOL-KO mice exhibit increased HCC burden. While control mice exhibit a dynamic regulation of FTO upon induction of liver damage, this response is abrogated in mice lacking FTO. Proteomic analyses revealed that liver damage-induced increases in FTO expression promotes m6A-demethylation of CUL4A reducing its protein expression. Functionally, knockdown of CUL4A restores the increased hepatocyte proliferation observed upon loss of FTO. Collectively, our study reveals a protective role for FTO-dependent dynamic m6A mRNA demethylation of CUL4A in the initiation of HCC development.

2020-11-03 | PXD018223 | Pride

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