Cloning and characterization of the 5 ' flanking region of the human uncoupling protein 3 (UCP3) gene

Uncoupling protein 3 (UCP3), a member of the UCP family, mainly expressed i n skeletal muscle could be responsible for thermogenesis in humans. Since l ittle is known about its regulation, we studied the 5' flanking region of t he human UCP3 (hUCP3) gene, which potentially contains the promoter sequenc es. We report the hUCP3 transcription initiation on a G located 764 nucleot ides upstream the A contained in the first translated codon. Therefore, hUC P3 first exon has 669 bases of untranslated sequence. We also report the cl oning and sequencing of seven kilobases from the gene 5' end and analyze th e features of the potential proximal promoter. The MyoD family binding moti f, 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 CAA T boxes. Additionally, three putative peroxisome proliferator and one thyro id 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. (C) 1999 Academic Press.