Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide maps of TCF7L1 binding during early adipogenesis

ABSTRACT: Here we show through genome-wide binding studies that transcription factor 7-like 1 (TCF7L1) represses structure-related genes during adipogenesis. Intriguingly, TCF7L1 is induced in a cell contact-dependent manner by confluency in preadipocytes and is required for adipocyte differentiation by repressing transcription of cell structure genes. TCF7L1 is also sufficient to bestow adipogenic potential upon non-adipogenic cells. These results implicate TCF7L1 as a novel adipogenic competency factor that uniquely determines adipogenic fate through cell structure organization required for adipocyte gene activation. Examination of TCF7L1 binding in preadipocytes treated for 24 hours with adipogenic stimuli.

ORGANISM(S): Mus musculus

SUBMITTER: Jonathan Schug

PROVIDER: E-GEOD-31867 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells.

Cristancho Ana G AG Schupp Michael M Lefterova Martina I MI Cao Shengya S Cohen Daniel M DM Chen Christopher S CS Steger David J DJ Lazar Mitchell A MA

Proceedings of the National Academy of Sciences of the United States of America 20110913 39

The identification of factors that define adipocyte precursor potential has important implications for obesity. Preadipocytes are fibroblastoid cells committed to becoming round lipid-laden adipocytes. In vitro, this differentiation process is facilitated by confluency, followed by adipogenic stimuli. During adipogenesis, a large number of cytostructural genes are repressed before adipocyte gene induction. Here we report that the transcriptional repressor transcription factor 7-like 1 (TCF7L1) b ...[more]

PMID: 21914845

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Project description:Visceral fat (VF) and subcutaneous fat (SF) are developmentally different tissues with different gene expression. Islet-1 (ISL1), a LIM-homeobox transcription factor with important developmental and regulatory function in islet, neural, and cardiac tissue, is virtually absent in SF but substantially expressed in the stromovascular [preadipocyte containing] fraction of VF; expression correlates negatively with adiposity in rodents and man. ISL1 expression is transiently increased in 3T3-L1 preadipocytes during early differentiation, suggesting a functional role. To examine the role of ISL1 in adipogenesis, we tested whether retroviral overexpression of ISL1 in 3T3-L1 preadipocytes affected their ability to differentiate into mature adipocytes. Terminal differentiation was assessed by Oil Red O [lipid droplet] staining and by immunoblot detection of adipocyte marker proteins, including aP2 and GLUT4. ISL1 significantly inhibited lipid droplet formation, reduced lipid accumulation (about 80% inhibition, p<0.05), and substantially inhibited aP2 and GLUT4 expression. ISL1 did not inhibit expression of C/EBPb and C/EBPd after induction of differentiation, but reduced PPARg and C/EBPa by >50% at both mRNA and protein level. In addition, the PPARg agonist, rosiglitazone, substantially rescued ISL1 inhibited adipogenesis in the absence of exogenous PPARg, and fully rescued in the presence of exogenous PPARg. In summary, ISL1 overexpression inhibited fat droplet formation, lipid accumulation, and adipocyte-specific gene expression; there was accompanying inhibition of C/EBPa, PPARg and downstream gene expression. We conclude that ISL1 overexpression inhibited adipocyte differentiation by inhibition of PPARg regulated gene expression. As abdominal obesity strongly correlates with insulin resistance, and cardiovascular risk, ISL1 up-regulation may impact abdominal obesity and its concomitant metabolic derangements. Total cellular RNA was isolated from 3T3-L1 cells expressing Flag-ISL1 or not at 48 h following treatment with differentiation cocktail. Individual RNA from biological triplicates was used for microarray analysis.

Dataset Information

Genome-wide maps of TCF7L1 binding during early adipogenesis

Publications

Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells.

Similar Datasets

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