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Molecular and Cellular Biology, February 2004, p. 1313-1323, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1313-1323.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Tissue-Selective, Bidirectional Regulation of PEX11{alpha} and Perilipin Genes through a Common Peroxisome Proliferator Response Element

Makoto Shimizu,1 Ayumi Takeshita,1 Toshiro Tsukamoto,1,{dagger} Frank J. Gonzalez,2 and Takashi Osumi1*

Department of Life Science, Graduate School of Science, Himeji Institute of Technology, Kamigori, Hyogo 678-1297, Japan,1 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922

Received 23 June 2003/ Returned for modification 6 August 2003/ Accepted 30 October 2003

Most cis-acting regulatory elements have generally been assumed to activate a single nearby gene. However, many genes are clustered together, raising the possibility that they are regulated through a common element. We show here that a single peroxisome proliferator response element (PPRE), located between the mouse PEX11{alpha} and perilipin genes, confers on both genes activation by peroxisome proliferator-activated receptor alpha (PPAR{alpha}) and PPAR{gamma}. A functional PPRE 8.4 kb downstream of the promoter of PEX11{alpha}, a PPAR{alpha} target gene, was identified by a gene transfection study. This PPRE was positioned 1.9 kb upstream of the perilipin gene and also functioned with the perilipin promoter. In addition, this PPRE, when combined with the natural promoters of the PEX11{alpha} and perilipin genes, conferred subtype-selective activation by PPAR{alpha} and PPAR{gamma}2. The PPRE sequence specifically bound to the heterodimer of RXR{alpha} and PPAR{alpha} or PPAR{gamma}2, as assessed by electrophoretic gel mobility shift assays. Furthermore, tissue-selective binding of PPAR{alpha} and PPAR{gamma} to the PPRE was demonstrated in hepatocytes and adipocytes, respectively, by chromatin immunoprecipitation assay. Hence, the expression of these genes is induced through the same PPRE in the liver and adipose tissue, where the two PPAR subtypes are specifically expressed.

* Corresponding author. Mailing address: Department of Life Science, Graduate School of Science, Himeji Institute of Technology, Kamigori, Hyogo 678-1297, Japan. Phone: 81-791-58-0192. Fax: 81-791-58-0193. E-mail: osumi{at}sci.himeji-tech.ac.jp.

{dagger} Present address: Genomics Research Institute, Utsunomiya University, Utsunomiya, Tochigi 321-8505, Japan.

Molecular and Cellular Biology, February 2004, p. 1313-1323, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.1313-1323.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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