The peroxisome proliferator response element (PPRE) present at positions -681/-669 in the rat liver 3-ketoacyl-CoA thiolase B gene functionally interacts differently with PPARalpha and HNF-4.
Although previous data showed that the putative thiolase B PPRE located at -681/-669 bind the PPARalpha-RXRalpha heterodimer in vitro (Kliewer et al. (1992) Nature 358, 771-774), there is no evidence about the functional role of this element. By gel mobility-shift assay, we found an interaction of this PPRE with not only PPARalpha but also with HNF-4. By transfection of cells with the putative PPRE-driven luciferase reporter vector and PPARalpha, we found no significant activation of the luciferase gene expression, in contrast to the case with reporter expression driven by the PPRE of the peroxisomal bifunctional enzyme. On the other hand, HNF-4 activated the luciferase gene expression driven by the putative thiolase PPRE. We suggest that the thiolase B gene induction by peroxisome proliferators employs either another PPRE or this one in combination with other gene regulatory element(s) to lead to the strong gene expression observed in the presence of peroxisome proliferators.
Nicolas-Frances
V
V
Université de Bourgogne, LBMC, 6, Boulevard Gabriel, Dijon, 21000, France.
Dasari
V K
VK
Abruzzi
E
E
Osumi
T
T
Latruffe
N
N
D000102:Acetyl-CoA C-Acyltransferase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D004247:DNA; D017931:DNA Primers; D004268:DNA-Binding Proteins; D017930:Genes, Reporter; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000201:enzymology*; D020025:Peroxisome Proliferators / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D020025:Peroxisome Proliferators; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004247:DNA; D000102:Acetyl-CoA C-Acyltransferase