Role of Sug1, a 19S proteasome ATPase, in the transcription of MHC I and the atypical MHC II molecules, HLA-DM and HLA-DO.

The 19S proteasome regulatory particle plays a critical role in cellular proteolysis. However, emerging evidence suggests roles for 19S proteasome subunits in regulating yeast and mammalian transcription. It has been previously shown that Sug1 is important for the transcription of MHC II molecules. We report here that Sug1 also has a role in regulating transcription of class I MHC and the MHC II-like molecules, HLA-DM and HLA-DO. Reduction of Sug1 expression causes a decrease in the transcription of MHC I and MHC II-like molecules. In addition, we show that association of Sug1 with MHC promoters is followed by the recruitment of the CREB-binding protein (CBP) and the class II transactivator (CIITA). Reduction of Sug1 expression is accompanied by decreased recruitment of CBP and CIITA to the MHC promoters and decreased histone H3 acetylation in these promoters. These studies suggest that Sug1 plays a critical role in transcription of MHC class I, and the MHC class II-like molecules, HLA-DM and HLA-DO.