Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response

Nat Commun. 2020 Nov 19;11(1):5898. doi: 10.1038/s41467-020-19579-y.


O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Cell Line, Tumor
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromosome Mapping
  • DNA Damage / genetics
  • DNA Damage / physiology*
  • Enhancer Elements, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Glycosylation
  • Humans
  • Nuclear Respiratory Factor 1 / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Proteomics


  • Chromatin
  • NRF1 protein, human
  • Nuclear Respiratory Factor 1
  • Acetylglucosamine