Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response.
Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response.
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O-GlcNAc 染色质相关蛋白的蛋白质组分析和全基因组图谱揭示了 O-GlcNAc 调节的基因毒性应激反应
DOI：
10.1038/s41467-020-19579-y
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发表时间：
2020-11-19
影响因子：
16.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Liu Y;Chen Q;Zhang N;Zhang K;Dou T;Cao Y;Liu Y;Li K;Hao X;Xie X;Li W;Ren Y;Zhang J
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 respiratory 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. Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1073/pnas.0811481106
发表时间：
2009-01-06
影响因子：
11.1
作者：
Laughlin, Scott T.;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
影响因子：
4.8
作者：
Banerjee, Sulagna;Sangwan, Veena;Saluja, Ashok K.
通讯作者：
Saluja, Ashok K.
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS
影响因子：
7.1
作者：
Fiaschetti G;Schroeder C;Castelletti D;Arcaro A;Westermann F;Baumgartner M;Shalaby T;Grotzer MA
通讯作者：
Grotzer MA