biostudies-literatureBoutant MNHLBI NIH HHSNIMH NIH HHSMedical Research CouncilEuropean Commission FP7e35810https://www.ebi.ac.uk/biostudies/studies/S-EPMC3351448biostudies-literatureUnknown7(5)<h4>Background</h4>The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that insulin represses NR2F2 gene expression in pancreatic β-cells. The cis-regulatory region of the NR2F2 promoter is unknown and its influence on metabolism in humans is poorly understood. The present study aimed to identify the regulatory regions that control NR2F2 gene transcription and to evaluate the effect of NR2F2 promoter variation on glucose homeostasis in humans.<h4>Methodology/principal findings</h4>Regulation of the NR2F2 promoter was assessed using gene reporter assays, ChIP and gel shift experiments. The effects of variation at SNP rs3743462 in NR2F2 on quantitative metabolic traits were studied in PloS oneGlucose-dependent regulation of NR2F2 promoter and influence of SNP-rs3743462 on whole body insulin sensitivity.PMC3351448G0801056BR01 HL087679R01 MH063706FP7_201413RL1 MH083268G05005395R01MH63706:025R01HL087679-02G10020841RL1MH083268-01Lecoeur CVaillant EScott DPhilippe JZhang PPerilhou AJarvelin MRVaxillaire MBalkau BBoutant MRamos OHVasseur-Cognet MValcarcel BFroguel PSebert SfalseGlucose-dependent regulation of NR2F2 promoter and influence of SNP-rs3743462 on whole body insulin sensitivity.<h4>Background</h4>The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that insulin represses NR2F2 gene expression in pancreatic β-cells. The cis-regulatory region of the NR2F2 promoter is unknown and its influence on metabolism in humans is poorly understood. The present study aimed to identify the regulatory regions that control NR2F2 gene transcription and to evaluate the effect of NR2F2 promoter variation on glucose homeostasis in humans.<h4>Methodology/principal findings</h4>Regulation of the NR2F2 promoter was assessed using gene reporter assays, ChIP and gel shift experiments. The effects of variation at SNP rs3743462 in NR2F2 on quantitative metabolic traits were studied in 2012-01-01T00:00:00Z20122026-05-01T08:31:23.266Z2025-06-27T03:05:57.457ZS-EPMC33514482260623610.1371/journal.pone.0035810