Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex

Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. Functional consequences of histone O-GlcNAcylation (O-GlcNAc=O-linked β-N-acetylglucosamine) are largely unexplored. Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post-translational modification. Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control.