The organization, promoter analysis, and expression of the human PPARgamma gene.

Details

Serval ID
serval:BIB_DA274DBE1C5A
Type
Article: article from journal or magazin.
Collection
Publications
Title
The organization, promoter analysis, and expression of the human PPARgamma gene.
Journal
Journal of Biological Chemistry
Author(s)
Fajas L., Auboeuf D., Raspé E., Schoonjans K., Lefebvre A.M., Saladin R., Najib J., Laville M., Fruchart J.C., Deeb S., Vidal-Puig A., Flier J., Briggs M.R., Staels B., Vidal H., Auwerx J.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
1997
Volume
272
Number
30
Pages
18779-18789
Language
english
Abstract
PPARgamma is a member of the PPAR subfamily of nuclear receptors. In this work, the structure of the human PPARgamma cDNA and gene was determined, and its promoters and tissue-specific expression were functionally characterized. Similar to the mouse, two PPAR isoforms, PPARgamma1 and PPARgamma2, were detected in man. The relative expression of human PPARgamma was studied by a newly developed and sensitive reverse transcriptase-competitive polymerase chain reaction method, which allowed us to distinguish between PPARgamma1 and gamma2 mRNA. In all tissues analyzed, PPARgamma2 was much less abundant than PPARgamma1. Adipose tissue and large intestine have the highest levels of PPARgamma mRNA; kidney, liver, and small intestine have intermediate levels; whereas PPARgamma is barely detectable in muscle. This high level expression of PPARgamma in colon warrants further study in view of the well established role of fatty acid and arachidonic acid derivatives in colonic disease. Similarly as mouse PPARgammas, the human PPARgammas are activated by thiazolidinediones and prostaglandin J and bind with high affinity to a PPRE. The human PPARgamma gene has nine exons and extends over more than 100 kilobases of genomic DNA. Alternate transcription start sites and alternate splicing generate the PPARgamma1 and PPARgamma2 mRNAs, which differ at their 5'-ends. PPARgamma1 is encoded by eight exons, and PPARgamma2 is encoded by seven exons. The 5'-untranslated sequence of PPARgamma1 is comprised of exons A1 and A2, whereas that of PPARgamma2 plus the additional PPARgamma2-specific N-terminal amino acids are encoded by exon B, located between exons A2 and A1. The remaining six exons, termed 1 to 6, are common to the PPARgamma1 and gamma2. Knowledge of the gene structure will allow screening for PPARgamma mutations in humans with metabolic disorders, whereas knowledge of its expression pattern and factors regulating its expression could be of major importance in understanding its biology.
Keywords
3T3 Cells, Adipose Tissue/chemistry, Adult, Animals, Base Sequence, Chromosome Mapping, Cloning, Molecular, Colon/chemistry, Gene Expression Regulation, Humans, Intestine, Small/chemistry, Kidney/chemistry, Mice, Microbodies/genetics, Molecular Sequence Data, Nuclear Proteins/genetics, Promoter Regions, Genetic, RNA, Messenger/metabolism, Receptors, Cytoplasmic and Nuclear/genetics, Restriction Mapping, Transcription Factors/genetics, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
07/03/2013 16:13
Last modification date
20/08/2019 15:59
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