Nicotinamide potentiates TSHR and MHC class II promoter activity in FRTL-5 cells

Here we show that nicotinamide modulates the promoter activity of rat thyrotropin (TSHR) and major histocompatibility complex (MHC) class II genes in rat FRTL-5 thyroid cells, and have identified a novel mechanism for its action. TSHR and MHC class II, are potentiated through reduced expression of a common repressor of these two genes, TSEP-1 (TSHR suppressor element binding protein-1)/YB-1. Thus we show that TSHR mRNA is increased and TSHR promoter activity was concentration-dependently activated from 0 to 40 mM nicotinamide. The promoter lengths of TSHR and MHC class II containing TSEP/YB-1 binding sites were enhanced by 40 mM nicotinamide, but not the ones deleted of these binding sites. TSEP-1/YB-1 binding to the recognition sites in both TSHR and MHC class II promoters was reduced in nicotinamide-treated FRTL-5 nuclear extracts. Nicotinamide reduced the expression of TSEP-1/YB-1 mRNA and TSEP-1/YB-1 protein in the nucleus.