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A new polymorphic site located in the human UCP1 gene controls the in vitro binding of CREB-like factor

Author:
Rousset, S., Gonzalez-Barroso, M. del Mar, Gelly, C., Pecqueur, C., Bouillaud, F., Ricquier, D., Cassard-Doulcier, A.M.
Source:
International journal of obesity 2002 v.26 no.5 pp. 735-738
ISSN:
0307-0565
Subject:
adenosine triphosphate, adipocytes, animal models, binding sites, brown adipose tissue, energy expenditure, genes, heat production, humans, obesity, point mutation, rodents, transcription (genetics), transcription factors, transfection
Abstract:
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.
Agid:
312806