O-GlcNAcylation in Transcriptional Regulation and Epigenetics

The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a unique intracellular glycosylation that mediates signal transduction. In this chapter, we will focus on its role on transcription. We will first review new methodologies to study chromatin-bound O-GlcNAcylated proteins. Then we will venture into different organisms, including flies, humans, and plants, and summarize the role of OGT in transcription. In flies, we will emphasize the role of O-GlcNAcylation in regulating the Polycomb Group (PcG), the Trithorax Group (TrxG), and the circadian rhythm. In humans, we will first cover the homeostatic regulation of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) and then will give a glimpse of the O-GlcNAcylated targets, such as RNA polymerase II, p53, and components of the Hippo pathway. We will give special attention to the glycosylated histone code, as it is an integral part of chromatin biology. Compared with humans, O-GlcNAcylation studies in plants are just getting started. We will delineate the distinct functions of SECRET AGENT (SEC) and SPINDLY (SPY) in vernalization, flowering, and gibberellin signaling. As more interdisciplinary techniques are entering the glycobiology field, we envision that more O-GlcNAcylated substrates will be revealed. And the marriage between chemistry and biology would surely solve the sweet enigma of O-GlcNAc.