© 2006 The Japanese Biochemical Society.
Regular Paper |
Peroxisome Proliferator–Activated Receptor Subtypes Differentially Cooperate with Other Transcription Factors in Selective Transactivation of the Perilipin/PEX11
Gene Pair
1 Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, Kamigori, Hyogo 678-1297; and 2 Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657
To whom correspondence should be addressed. Tel: +81-791-58-0192, Fax: +81-791-58-0193, E-mail: osumi{at}sci.u-hyogo.ac.jp
Perilipin is an adipocyte-specific protein associated with lipid droplets that is crucial for the regulation of storage and mobilization of lipids. We earlier reported that the mouse perilipin gene is regulated by peroxisome proliferator–activated receptor (PPAR) 
through a peroxisome proliferator–response element (PPRE) positioned upstream of the perilipin promoter. Moreover, we showed that this PPRE also controls expression of the PEX11
gene, which is located further upstream. We show here that three elements, A, B, and C, in close proximity downstream of the PPRE, are essential for transactivation of the perilipin gene by PPAR. Electrophoretic gel-mobility shift assays demonstrated that nuclear factor (NF)-1 subtypes bind specifically to element B. Furthermore, chromatin immunoprecipitation using 3T3-L1 cells revealed that NF-1A and NF-1B bind to element B in a differentiation-dependent fashion, whereas binding is constitutive with NF-1C and NF-1X. Element C is likely to be a binding motif for nuclear receptors. With PPAR, elements A–C do not appear to be required for transactivation of the PEX11 gene, so that cooperation with other transcription factors may be differentially involved in selective transactivation of the PEX11 and perilipin genes by different PPAR subtypes.
* Present address: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.