A new polymorphic site located in the human UCP1 gene controls the in vitro binding of CREB-like factor.
Uncoupling protein 1 (UCP1) is uniquely expressed in brown adipose tissue (BAT) and generates heat by uncoupling respiration from ATP synthesis. A defect in BAT thermogenesis has been described in different models of rodent obesity. In humans, the implication of BAT in energy expenditure is still under discussion. A BclI polymorphism associated with fat gain over time has been described in the upstream region of the human UCP1 (hUCP1) gene. In this study, a new polymorphic site linked to the BclI site is described which results in a C to A point mutation, 89 bp downstream of the BclI site, ie at position -3737 bp. This site is located in the recently analysed regulatory region of the hUCP1 gene. The mutation disrupts a consensus site for the binding of ATF/CREB transcription factor family and inhibits the factor binding in vitro. However, transient transfection of a rodent brown adipocyte cell line shows that the isoproterenol (ISO) stimulation of the hUCP1 gene transcription is not significantly affected by this mutation. However, we postulate that the C/A substitution, in human, may contribute to a minor defect in the regulation of hUCP1 transcription and that would explain fat gain over time.
Rousset
S
S
Centre de Recherches sur l'Endocrinologie Moléculaire et le Développement, CNRS, Meudon, France.
del Mar Gonzalez-Barroso
M
M
Gelly
C
C
Pecqueur
C
C
Bouillaud
F
F
Ricquier
D
D
Cassard-Doulcier
A-M
AM
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007473:Ion Channels; D007545:Isoproterenol / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D024101:Mitochondrial Proteins; D016296:Mutagenesis; D011110:Polymorphism, Genetic; D014162:Transfection; D000071256:Uncoupling Protein 1
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D004247:DNA; D000242:Cyclic AMP; D007545:Isoproterenol