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Cloning and Characterization of the 5′ Flanking Region of the Human Uncoupling Protein 3 (UCP3) Gene,☆☆

https://doi.org/10.1006/bbrc.1999.0530Get rights and content

Abstract

Uncoupling protein 3 (UCP3), a member of the UCP family, mainly expressed in skeletal muscle could be responsible for thermogenesis in humans. Since little is known about its regulation, we studied the 5′ flanking region of the human UCP3 (hUCP3) gene, which potentially contains the promoter sequences. We report the hUCP3 transcription initiation on a G located 764 nucleotides upstream the A contained in the first translated codon. Therefore, hUCP3 first exon has 669 bases of untranslated sequence. We also report the cloning and sequencing of seven kilobases from the gene 5′ end and analyze the features of the potential proximal promoter. The MyoD family binding motif, called E-box, is the most abundant on this region. Other muscle-specific motives present in the potential proximal promoter include a MEF2 site as well as binding sequences for ubiquitous factors such as GC box and two CAAT boxes. Additionally, three putative peroxisome proliferator and one thyroid hormone response elements (PPRE and TRE, respectively) are found, which suggest a potential role for the peroxisome proliferator-activated receptor (PPAR) and thyroid hormone in human UCP3 gene expression. The description of the promoter region of the UCP3 gene will facilitate the elucidation of its transcriptional control.

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    The 5′ flanking nucleotide sequence of the human UCP3 gene reported in this article is available on the GenBank database under Accession No. AF127916.

    ☆☆

    Abbreviations used: ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cDNA, complementary deoxyribonucleic acid; dNTP, deoxynucleotide triphosphate; DR, direct repeat; DTT, dithiothreitol; EDTA, ethylendiaminetetraacetic acid; EST, expressed sequenced tags; Mops, 3-[N-morpholino]propanesulfonic acid; nt, nucleotide; Pipes, piperazine-N,N′-bis[2-ethanesulfonic acid]; PPAR, peroxisome proliferator activated receptor; PCR, polymerase chain reaction; RACE, rapid amplification of cDNA ends; RT, reverse transcription; SDS, sodium dodecyl sulfate; SSC, standard saline citrate

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