Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that decreases the expression of class II MHC Ag in the melanoma cell line Hs294T(c). To investigate the mechanism of this repression, we have examined the effect of TGF-β1 on expression of the HLA-DRα gene. Both the constitutive level of HLA-DR protein and DRα mRNA were repressed by treatment with TGF-β1. The proximal 176 bp of the DRα promoter were sufficient to confer TGF-β1 repression on a reporter gene. Deletional and mutational analysis of the DRα promoter revealed that the conserved S and X1 promoter elements were important for basal expression of DRα and also mediated the down-regulation by TGF-β1. Mobility shift assays and in vivo footprinting showed no change in occupancy of the proximal DRα promoter after TGF-β1 treatment. These results identify the DNA elements that mediate repression of the HLA-DRα gene by TGF-β1 and suggest that TGF- β1 acts at these sites without causing a change in promoter occupancy.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Immunology|
|State||Published - 1993|
ASJC Scopus subject areas
- Immunology and Allergy