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 c1 and t he adenine nucleotide translocator-2 (ANT2) in adult rat liver. Here w e show that T3 activates expression of a reporter gene driven from the human cytochrome c1 and ANT2 promoters transfected into human chorioc arcinoma JEG3 cells. By contrast, the human F1-ATPase beta-subunit pro moter responded marginally, thus providing a pattern of differential e xpression similar to that earlier observed in rats in vivo. T3-activat ion is dependent on co-expression of the thyroid hormone receptor (TR alpha 1). Co-expression of both the TR and RXR receptors had no additi onal effect. Transient transfection of deletion constructs showed that T3 activation is retained by the proximal regions of the cytochrome c 1 and ANT2 promoters, and, in the case of cytochrome c1, is lost upon removal of a fragment containing the transcription initiator ((nucleot ides) (nt) + 1 to + 100). The promoter regions supporting T3-activatio n of the reporter genes appear to lack strong DNA binding sites for TR and retinoid X receptor (RXR). (C) 1997 Elsevier Science Ireland Ltd.