Title

The identification and characterization of a STAT 1 binding site in the PPARγ2 promoter

Document Type

Article

Publication Date

9-21-2001

Abstract

Interferon-γ (IFNγ) has been shown to decrease the expression of peroxisome proliferator activated receptor-γ (PPARγ) in fat cells by blocking the synthesis and increasing the degradation of this transcription factor. Since IFNγ is a potent activator of STAT 1, we searched for IFNγ-sensitive binding sites in the PPARγ promotors. A region of the murine PPARγ2 promoter was identified that bound nuclear protein from adipocyte nuclei that had been acutely treated with IFNγ. Supershift analysis revealed that STAT 1, and no other STATs present in the adipocyte nucleus, was capable of binding to this site within the PPARγ2 promoter. NIH 3T3 and 3T3-L1 cells were transiently transfected with a PPARγ2 promoter reporter construct, which contained the STAT 1 binding site. Treatment of these cells with IFNγ resulted in a decrease in reporter activity, demonstrating the modulation of the PPARγ2 promoter by IFNγ. We also examined the ability of leukemia inhibitory factor (LIF) to regulate binding at this site. LIF, a potent activator of STAT3 and a weak activator of STAT 1 in these cells, resulted in some binding to the IFNγ responsive element in the PPARγ2 promoter that was mediated by STAT 1. Therefore, we examined the ability of LIF to regulate PPARγ mRNA and observed that LIF, unlike IFNγ, had little effect on PPARγ expression. These results and our previous work suggest that cytokine induced STAT 1 homodimers modulate the transcriptional repression of PPARγ2 in adipocytes. © 2001 Academic Press.

Publication Source (Journal or Book title)

Biochemical and Biophysical Research Communications

First Page

484

Last Page

492

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