Cellular homeostasis is ensured by myriad cellular processes that integrate environmental changes and maintain stability within the organism. Variation in nutrient availability can be reflected by the post-translational modification of many proteins by the nutrient sensor O-GlcNAcylation. Herein, we describe a molecular mechanism of transcription regulation by O-GlcNAcylation of the TATA-box binding protein (TBP). We show that O-GlcNAcylation regulates its interaction with BTAF1, hence, formation of the B-TFIID complex, and its dynamic cycling on and off of DNA. We mapped three O-GlcNAcylation sites at the N-terminus of TBP and defined T114 as a main regulator of the interaction with BTAF1. CRISPR/Cas9 editing of wild-type TBP replaced by a T114A mutant, leads to profound modification of HeLa cells glucose and lipid metabolism and gene expression profile. These data indicate that basal transcription machinery, via O-GlcNAcylation of TBP, can integrate nutrient availability and modulate the transcriptome, resulting in adaptation of cellular metabolism. SOURCE: Gerald,W,HartHart Lab Johns Hopkins School of Medicine

Pluto Bioinformatics

GSE106231: O-GlcNAcylation of human TATA-Box binding protein is required to sustain key metabolic enzyme gene expression