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

Nature Communications
Yubo LiuJianing Zhang

Abstract

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 expres...Continue Reading

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Citations

May 22, 2021·Biochimica Et Biophysica Acta. General Subjects·Xueqin XieYubo Liu

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Datasets Mentioned

BETA
GSE91992
GSE141698

Methods Mentioned

BETA
immunoprecipitation
proteomic profiling
ChIP
RNA-seq
COGC-seq
ChIP-seq
co-IP
PCR
glycosylation
co-immunoprecipitation

Software Mentioned

Homer
MACS2
beanplot
STRING
BGISEQ
RSEM
Samtools
GraphPad Prism
iProX
500

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