Upstream stimulating factor-1 mediates the E-box-dependent transcriptional repression of the plasminogen activator inhibitor-1 gene in human mast cells.
Plasminogen activator inhibitor (PAI)-1 promotes development of asthma. PAI-1 mRNA and protein are markedly induced in activated mast cells (MCs), a major effector cell type in asthma. However, regulatory mechanisms of PAI-1 transcription in MCs are unknown. We present first evidence that PAI-1 is transcriptionally regulated in human MCs (hMCs). In addition to three enhancer regions, we demonstrated that the E-box at -566 bp to -561 bp is the negative regulatory element, and the specific and constitutive binding of the upstream stimulating factor-1 to this E-box is the key mechanism of the negative regulation of PAI-1 expression in hMCs.
Ma
Zhongcai
Z
University of California, Los Angeles, UCLA School of Medicine, Division of Allergy and Immunology, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, United States.
Jhun
BongSook
B
Oh
Chad K
CK
D002460:Cell Line; D024721:E-Box Elements / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D051720:Upstream Stimulatory Factors / Q000235:genetics* / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D011993:Recombinant Fusion Proteins; D051720:Upstream Stimulatory Factors; D015759:Ionomycin; D008156:Luciferases