Thyroid hormone activates transcription from the promoter regions of some human nuclear-encoded genes of the oxidative phosphorylation system.
Thyroid hormone (T3) modulates the mRNA levels for cytochrome c and the adenine nucleotide translocator-2 (ANT2) in adult rat liver. Here we show that T3 activates expression of a reporter gene driven from the human cytochrome c1 and ANT2 promoters transfected into human choriocarcinoma JEG3 cells. By contrast, the human F1-ATPase beta-subunit promoter responded marginally, thus providing a pattern of differential expression similar to that earlier observed in rats in vivo. T3-activation is dependent on co-expression of the thyroid hormone receptor (TR alpha1). Co-expression of both the TR and RXR receptors had no additional effect. Transient transfection of deletion constructs showed that T3 activation is retained by the proximal regions of the cytochrome c1 and ANT2 promoters, and, in the case of cytochrome c1, is lost upon removal of a fragment containing the transcription initiator ((nucleotides) (nt) + 1 to + 100). The promoter regions supporting T3-activation of the reporter genes appear to lack strong DNA binding sites for TR and retinoid X receptor (RXR).
Li
R
R
Department of Biochemistry, Stockholm University, Sweden.
Luciakova
K
K
Zaid
A
A
Betina
S
S
Fridell
E
E
Nelson
B D
BD
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002822:Choriocarcinoma; D003575:Cytochromes c1 / Q000096:biosynthesis*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008099:Liver / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000096:biosynthesis*; D010085:Oxidative Phosphorylation; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D011993:Recombinant Fusion Proteins; D014284:Triiodothyronine; D003575:Cytochromes c1; D000226:Mitochondrial ADP, ATP Translocases