J. Biochem, 1998, Vol. 123, No. 6 1174-1179
© 1998 Japanese Biochemical Society
research-article |
Functional Interactions between Nuclear Receptors Recognizing a Common Sequence Element, the Direct Repeat Motif Spaced by One Nucleotide (DR-1)1
Department of Life Science, Faculty of Science, Himeji Institute of Technology Kamigori, Hyogo 678-1297
3To whom correspondence should be addressed. Tel: +81-7915-8-0192, Fax: +81-7915-8-0193, E-mail: osumi{at}sci.himeji-tech.ac.jp
Direct repeat motifs composed of two hexamer half-sites spaced by a single nucleotide (DR-1) are recognized by several members of the nuclear hormone receptor superfamily. We examined, by means of gene transfection assays, the interplay between the DR-1-binding nuclear receptors commonly expressed in liver, peroxisome proliferator-activated receptor a (PPAR
), hepatocyte nuclear factor-4 (HNF-4), and chicken ovalbumin upstream transcription factor I (COUP-TFI). Both PPAR and HNF-4 efficiently bound to the acyl-CoA oxidase gene enhancer element, but PPAR exhibited much stronger transactivation than HNF-4. As a result, HNF-4 suppressed the gene-activating function of PPAR, when they were expressed together, due to competition for a common binding site. On the other hand, HNF-4, but not PPAR, effectively bound to the apolipoprotein CIII gene element, and activated gene transcription. PPAR had no effect even when co-expressed with HNF-4. COUP-TFI bound to both elements, and suppressed the gene activation by PPAR and HNF-4. Thus, these nuclear receptors have individual functions in gene regulation, and exhibit complex compound effects when they co-exist.
1 This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and a grant from the ONO Medical Research Foundation.
2 Present address: Division of Molecular Science, the Graduate School of Science and Technology, Kobe University, Nada-ku, Kobe 657-8501.
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