STAT 1 binds to the LPL promoter in vitro.
Interferon-gamma (IFNgamma) has been shown to decrease the expression and activity of lipoprotein lipase (LPL). Hence, we searched for IFNgamma sensitive binding sites within the murine LPL promoter. A region of the LPL promoter was identified that specifically binds nuclear, but not cytosolic, extracts isolated from IFNgamma-treated 3T3-L1 adipocytes. EMSA analysis revealed that two protein complexes bind to this site within the LPL promoter and supershift analysis demonstrated that both of these complexes contained STAT 1 proteins. In addition, we have shown that this effect is specific for IFNgamma, since LIF treatment, which also induces STAT 1, did not confer binding to this site. Interestingly, binding to this site within the LPL promoter could be effectively competed with a STAT 1 binding site that we previously identified in the PPARgamma2 promoter. Also, IFNgamma treatment resulted in decreased levels of LPL protein. In summary, we have identified a STAT 1 binding site within the murine LPL promoter which likely plays a role in the IFNgamma induced decrease of LPL expression.
Hogan
Jessica C
JC
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Stephens
Jacqueline M
JM
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006131:Growth Inhibitors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D046911:Macromolecular Substances; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma; D008071:Lipoprotein Lipase