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

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

PROVIDER: PRJNA230260 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1040800.fastq.gz	Fastqsanger.gz
	SRR1040801.fastq.gz	Fastqsanger.gz
	SRR1040802.fastq.gz	Fastqsanger.gz
	SRR1040803.fastq.gz	Fastqsanger.gz
	SRR1040804.fastq.gz	Fastqsanger.gz

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Similar Datasets

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

2014-02-24 | GSE52830 | GEO

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

Project description:Genome-wide association studies (GWAS) have reproducibly associated variants within introns of FTO with increased risk for obesity and type 2 diabetes (T2D). Although 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. However, no direct connection between the obesity-associated variants and FTO expression or function has been made. Here we show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, with the homeobox gene IRX3. The obesity-associated FTO region directly interacts with the promoters of IRX3 as well as FTO in the human, mouse and zebrafish genomes. Furthermore, long-range enhancers within this region recapitulate aspects of IRX3 expression, suggesting that the obesity-associated interval belongs to the regulatory landscape of IRX3. Consistent with this, obesity-associated single nucleotide polymorphisms are associated with expression of IRX3, but not FTO, in human brains. A direct link between IRX3 expression and regulation of body mass and composition is demonstrated by a reduction in body weight of 25 to 30% in Irx3-deficient mice, primarily through the loss of fat mass and increase in basal metabolic rate with browning of white adipose tissue. Finally, hypothalamic expression of a dominant-negative form of Irx3 reproduces the metabolic phenotypes of Irx3-deficient mice. Our data suggest that IRX3 is a functional long-range target of obesity-associated variants within FTO and represents a novel determinant of body mass and composition.

| S-EPMC4113484 | biostudies-literature

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

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

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

Project description:Oncogenes can be activated in cis through multiple mechanisms including enhancer hijacking events and noncoding mutations that create enhancers or promoters de novo. These paradigms have helped parse somatic variation of noncoding cancer genomes, thereby providing a rationale to identify noncanonical mechanisms of gene activation. Here we describe a novel mechanism of oncogene activation whereby focal copy number loss of an intronic element within the FTO gene leads to aberrant expression of IRX3, an oncogene in T cell acute lymphoblastic leukemia (T-ALL). Loss of this CTCF bound element downstream to IRX3 (+224 kb) leads to enhancer hijack of an upstream developmentally active super-enhancer of the CRNDE long noncoding RNA (-644 kb). Unexpectedly, the CRNDE super-enhancer interacts with the IRX3 promoter with no transcriptional output until it is untethered from the FTO intronic site. We propose that 'promoter tethering' of oncogenes to inert regions of the genome is a previously unappreciated biological mechanism preventing tumorigenesis.

2024-10-20 | GSE279521 | GEO

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

2024-10-20 | GSE279520 | GEO

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

2024-10-20 | GSE279517 | GEO

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

RNA Sequencing of mouse E15.5 Six2-Cre; Irx3/5(loxP/loxP) whole kidneys

Project description:Transcriptional profiling of E15.5 whole kidneys with a conditional deletion of Irx3/5 in the nephron progenitor cell lineage. Irx3/5 were conditionally deleted using Six2-driven Cre-recombinase. Data will provide novel insight into the functional contributions of Irx3/5 towards nephrogenesis.

2024-07-23 | GSE271904 | GEO

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