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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Genetics

NR2F2 recognition of DNA motifs is considered promiscuous (see the TFBS section). Consequently, a wide range of targets can be modulated by this nuclear receptor and its dysfunction is linked to several pathologies related to the circulatory system[1][2][3] and heart defects[4], digestive system[5][6], reproductive system[2][7][8][9], nervous system[10][11], skeletal muscles development[12], insulin secretion, glucose and lipid metabolism[13][14][15] (see above phenotype terms list). NR2F2 homozygous invalidation in mice leads to embryonic lethality at day 10 (E10)[2] while heterozygous invalidation is lethal to 2/3 of progeny before weaning[2]. Recently, it was found that subjects of the French DESIR population who carried the rs3743462 T-to-C polymorphism, located in the distal glucose-responsive promoter, displayed lower basal insulin levels and lower HOMA-IR index (Boutant et al. Glucose-dependent regulation of NR2F2 promoter and influence of SNP-rs3743462 on whole body insulin sensitivity. PloS ONE. accepted).

References
  1. Pereira FA et al. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev., 13(8):1037-49. (PMID 10215630)
  2. Pereira FA et al. COUP-TF orphan nuclear receptors in development and differentiation. Cell. Mol. Life Sci., 57(10):1388-98. (PMID 11078018)
  3. You LR et al. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature, 435(7038):98-104. (PMID 15875024)
  4. Nakamura E et al. 5.78 Mb terminal deletion of chromosome 15q in a girl, evaluation of NR2F2 as candidate gene for congenital heart defects. Eur J Med Genet, 54(3):354-6. (PMID 21172461)
  5. Takamoto N et al. COUP-TFII is essential for radial and anteroposterior patterning of the stomach. Development, 132(9):2179-89. (PMID 15829524)
  6. You LR et al. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc. Natl. Acad. Sci. U.S.A., 102(45):16351-6. (PMID 16251273)
  7. Takamoto N et al. Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction. Mol. Endocrinol., 19(9):2299-308. (PMID 15890675)
  8. Kurihara I et al. COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity. PLoS Genet., 3(6):e102. (PMID 17590085)
  1. Petit FG et al. Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to placental deficiency. Proc. Natl. Acad. Sci. U.S.A., 104(15):6293-8. (PMID 17404209)
  2. Naka H et al. Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development. Nat. Neurosci., 11(9):1014-23. (PMID 19160499)
  3. Lutz B et al. Developmental regulation of the orphan receptor COUP-TF II gene in spinal motor neurons. Development, 120(1):25-36. (PMID 8119130)
  4. Lee CT et al. The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle development. Mol. Cell. Biol., 24(24):10835-43. (PMID 15572686)
  5. Bardoux P et al. Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout. Diabetes, 54(5):1357-63. (PMID 15855320)
  6. Perilhou A et al. The transcription factor COUP-TFII is negatively regulated by insulin and glucose via Foxo1- and ChREBP-controlled pathways. Mol. Cell. Biol., 28(21):6568-79. (PMID 18765640)
  7. Li L et al. The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism. Cell Metab., 9(1):77-87. (PMID 19117548)
MeSH cloud (automatically populated)
About this section
The MeSH cloud below displays MeSH terms that are associated with this transcription factor. The physical size of the terms reflect the significance of their association with the transcription factor as determined by the Fisher's Exact Test. It should be noted that these associations do not necessarily imply a positive correlation between the described MeSH term and this transcription factor. For instance, if the MeSH term "apoptosis" occurs, it may indicate that this transcription factor can induce apoptosis (positive correlation), or prevent apoptosis (negative correlation). Methods: The transcription factor is mapped to a set of Pubmed publications through the gene-to-pubmed association as provided by NCBI. Then, a collection of MeSH terms associated with the papers are compiled, along with the frequency of each MeSH term. The Fisher's Exact Test is conducted on the frequency of each term in the collection, versus its average frequency, to determine its significance in the collection. More information on MeSH can be found on the MeSH homepage.
MeSH term Fisher's exact p-value
1 Carcinoma, Hepatocellular 0.0025
2 Cell Transformation, Viral 0.021
3 Neuroblastoma 0.034
4 Coronary Artery Disease 0.037
5 Crohn Disease 0.039
MeSH term Fisher's exact p-value
1 Carcinoma, Hepatocellular 0.0025
2 Liver Neoplasms 0.012
3 Colorectal Neoplasms 0.015
4 Intestinal Neoplasms 0.020
5 Cell Transformation, Viral 0.021
6 Digestive System Neoplasms 0.023
7 Colonic Diseases 0.025
8 Intestinal Diseases 0.028
9 Neuroblastoma 0.034
10 Neuroectodermal Tumors, Primitive, Peripheral 0.036
11 Coronary Artery Disease 0.037
12 Crohn Disease 0.039
13 Neuroectodermal Tumors, Primitive 0.045
MGI mammalian phenotype terms (automatically populated)
abnormal heart tube morphology (MP:0000270) incomplete somite formation (MP:0001689) hemorrhage (MP:0001914) absent ventricular trabeculae (MP:0000296) abnormal vein morphology (MP:0002725) decreased angiogenesis (MP:0005602) embryonic lethality during organogenesis (MP:0006207) abnormal anterior cardinal vein morphology (MP:0004784) abnormal posterior cardinal vein morphology (MP:0004785) decreased body size (MP:0001265) postnatal lethality (MP:0002082) perinatal lethality (MP:0002081) prenatal lethality (MP:0002080) abnormal glucose homeostasis (MP:0002078) abnormal lipid level (MP:0001547) increased circulating insulin level (MP:0002079) increased circulating triglyceride level (MP:0001552) decreased fatty acid level (MP:0005282) impaired glucose tolerance (MP:0005293) insulin resistance (MP:0005331) decreased circulating glucose level (MP:0005560) decreased insulin secretion (MP:0003059) increased insulin secretion (MP:0003058) abnormal stomach morphology (MP:0000470) abnormal stomach epithelium morphology (MP:0000471) abnormal stomach glandular epithelium morphology (MP:0000473) abnormal enteric neuron morphology (MP:0001046) small stomach (MP:0002691) abnormal digestive system development (MP:0003119) abnormal gastric parietal cell morphology (MP:0004139) abnormal blood vessel morphology (MP:0001614) abnormal estrous cycle (MP:0001927) abnormal ovary morphology (MP:0001126) postnatal growth retardation (MP:0001732) decreased litter size (MP:0001935) reduced female fertility (MP:0001923) delayed vaginal opening (MP:0002636) decreased circulating progesterone level (MP:0005185) prolonged diestrus (MP:0009011) prolonged metestrus (MP:0009020) absent estrus (MP:0009021) abnormal uterine horn morphology (MP:0009085) impaired embryo implantation (MP:0001729) edema (MP:0001785) abnormal placenta development (MP:0001712) absent placental labyrinth (MP:0003403) abnormal uterine environment (MP:0004014) abnormal spontaneous abortion rate (MP:0004244) abnormal maternal decidual layer morphology (MP:0004256) abnormal myometrium morphology (MP:0008256) embryonic lethality (MP:0008762) abnormal placental labyrinth vasculature morphology (MP:0008803) abnormal spongiotrophoblast cell morphology (MP:0008959) short uterine horn (MP:0009089) increased trophoblast giant cell number (MP:0009397) abnormal eye development (MP:0001286) microphthalmia (MP:0001297) abnormal retinal pigment epithelium morphology (MP:0005201) coloboma (MP:0005262) abnormal optic stalk morphology (MP:0004268) abnormal optic disc morphology (MP:0008259) abnormal lymphatic vessel morphology (MP:0001879)