Abstract
Down-regulation of the MHC class I enhancer in tumorigenic Ad12 cells is associated with strong binding of COUP-TF and negligible binding of activator NF-kappaB. By comparison, in nontumorigenic Ad5 cells, class I expression is high due to negligible binding of COUP-TF and strong binding of NF-kappaB. Here, we show that COUP-TFII, but not COUP-TFI, is expressed in Ad12-transformed cells. The dramatically stronger DNA binding of COUP-TFII to the class I enhancer in Ad12- compared to Ad5-transformed cells correlates with higher COUP-TFII promoter activity and higher levels of COUP-TFII mRNA and protein. Significantly, NF-kappaB p50/p52 double-knockout cells enabled us to demonstrate directly that COUP-TFII can completely repress both nonactivated and NF-kappaB-activated MHC class I transcription.
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