| The goal of these studies was to identify novel O-GlcNAc Transferase (OGT) binding partners in hopes of determining how OGT maintains substrate specificity. With so many known O-GlcNAcylated proteins, the inherent problem for OGT is to correctly identify proteins based on extracellular and on intracellular cues. In these studies we show that 1) the interaction between OGT and Coactivator Associated Arginine Methyltransferase 1 (CARM1) directs OGT to certain substrates, 2) histones are O-GlcNAcylated and their O-G1cNAcylation can change in response to stimuli, 3) CARM1 targets OGT to O-GlcNAcylate histones, 4) OGT over-expression affects mitotic chromatin dynamics, and 5) the altered chromatin dynamics observed with OGT over-expression is due partly to its association with CARM1. Taken together, these studies show that a CARM1:OGT complex targets OGT to substrates. Additionally, we show that OGT can directly and indirectly modify the histone code through modifying histones or by modulating the ability of chromatin remodelers to recognize their substrates. These findings present advances in our understanding not only of chromatin biology, but how OGT can regulate nuclear architecture. |
