Skip to Main content Skip to Navigation
Journal articles

Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences.

Abstract : AIMS/HYPOTHESIS: Uncoupling protein (UCP) 3 is an inner mitochondrial membrane transporter mainly produced in skeletal muscle in humans. UCP3 plays a role in fatty acid metabolism and energy homeostasis and modulates insulin sensitivity. In humans, UCP3 content is higher in fast-twitch glycolytic muscle than in slow-twitch oxidative muscle and is dysregulated in type 2 diabetes. Here, we studied the molecular mechanisms determining human UCP3 levels in skeletal muscle and their regulation by fasting in transgenic mice. METHODS: We produced a series of transgenic lines with constructs bearing different putative regulatory regions of the human UCP3 gene, including promoter and intron sequences. UCP3 mRNA and reporter gene expression and activity were measured in different skeletal muscles and tissues. RESULTS: The profile of expression and the response to fasting and thyroid hormone of human UCP3 mRNA in transgenic mice with 16 kb of the human UCP3 gene were similar to that of the endogenous human gene. Various parts of the UCP3 promoter did not confer expression in transgenic lines. Inclusion of intron 1 resulted in an expression profile in skeletal muscle that was identical to that of human UCP3 mRNA. Further dissection of intron 1 revealed that distinct regions were involved in skeletal muscle expression, distribution among fibre types and response to fasting. CONCLUSIONS/INTERPRETATION: The control of human UCP3 transcription in skeletal muscle is not solely conferred by the promoter, but depends on several cis-acting elements in intron 1, suggesting a complex interplay between the promoter and intronic sequences.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00410139
Contributor : Marie Francoise Simon <>
Submitted on : Tuesday, August 18, 2009 - 9:04:01 AM
Last modification on : Monday, September 21, 2020 - 4:24:02 PM

Links full text

Identifiers

Collections

Citation

Amandine Girousse, Geneviève Tavernier, Claire Tiraby, L. Lichtenstein, Jason Iacovoni, et al.. Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences.. Diabetologia, Springer Verlag, 2009, 52 (8), pp.1638-46. ⟨10.1007/s00125-009-1385-9⟩. ⟨inserm-00410139⟩

Share

Metrics

Record views

118