Show simple item record

dc.contributor.authorSolanes, Gemma
dc.contributor.authorPedraza González, Neus
dc.contributor.authorCalvo Garrido, Verónica
dc.contributor.authorVidal Puig, Antonio
dc.contributor.authorLowell, Bradford B.
dc.contributor.authorVillarroya, Francesc
dc.date.accessioned2017-01-18T13:25:04Z
dc.date.issued2005
dc.identifier.issn0264-6021
dc.identifier.urihttp://hdl.handle.net/10459.1/59026
dc.description.abstractThe transcription of the human UCP3 (uncoupling protein-3) gene in skeletal muscle is tightly regulated by metabolic signals related to fatty acid availability. However, changes in thyroid status also modulate UCP3 gene expression, albeit by unknown mechanisms. We created transgenic mice bearing the entire human UCP3 gene to investigate the effect of thyroid hormones on human UCP3 gene expression. Treatment of human UCP3 transgenic mice with thyroid hormones induced the expression of the human gene in skeletal muscle. In addition, transient transfection experiments demonstrate that thyroid hormones activate the transcription of the human UCP3 gene promoter when MyoD and the TR (thyroid hormone receptor) were co-transfected. The action of thyroid hormones on UCP3 gene transcription is mediated by the binding of the TR to a proximal region in the UCP3 gene promoter that contains a direct repeat structure. An intact DNA sequence of this site is required for thyroid hormone responsiveness and TR binding. Chromatin immunoprecipitation assays revealed that the TRbinds this element in vivo. The murine Ucp3 gene promoter was also dependent on MyoD and responsive to thyroid hormone in transient transfection assays. However, it was much less sensitive to thyroid hormone than the human UCP3 promoter. In summary, UCP3 gene transcription is activated by thyroid hormone treatment in vivo, and this activation is mediated by a TRE (thyroid hormone response element) in the proximal promoter region. Such regulation suggests a link between UCP3 gene expression and the effects of thyroid hormone on mitochondrial function in skeletal muscle.ca_ES
dc.description.sponsorshipThis work was supported by grant SAF2002-03648 from Ministerio de Ciencia y Tecnolog´ıa, Fundaci´o la Marat´o de TV3 and grant C03/08 from Instituto Carlos III, Ministerio de Sanidad y Consumo, Spain. G. S. is under the ‘Ramon y Cajal’ Investigator program. We thank Dr R. Evans, Dr H. H. Samuels, Dr H. C. Towle and Dr A. B. Lassar for kindly supplying expression vectors.ca_ES
dc.language.isoengca_ES
dc.publisherPortland Pressca_ES
dc.relationMICYT/PN2000-2003/SAF2002-03648ca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1042/BJ20041073ca_ES
dc.relation.ispartofBiochemical Journal, 2005, vol. 386, núm. 3, p. 505-513ca_ES
dc.rights(c) Biochemical Society, 2005ca_ES
dc.subjectPromoter regulationca_ES
dc.subjectThyroid hormoneca_ES
dc.subjectTransgenic mouseca_ES
dc.subjectUncoupling protein-3 (UCP3)ca_ES
dc.titleThyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter regionca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1042/BJ20041073
dc.date.embargoEndDate2025-01-01


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record