Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin associated proteins reveals O-GlcNAc-regulated genotoxic stress response in human breast cancer cells
作者单位：School of Life and Pharmaceutical SciencesDalian University of Technology Clinical Laboratory of BGI HealthBGI-Shenzhen
会议名称：《2020年糖科学青年科技论坛》
会议日期：2020年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：O-GlcNAc genotoxic stress transcriptional network NRF1
摘 要：O-GlcNAc modification plays a critical role in regulating stress response program and cellular ***,systematic and multi-omics studies on O-GlcNAc regulated mechanism during these processes have been *** this study,multi-layered data were obtained by an emerging chemical reporter-based method to integrally survey O-GlcNAc function in genotoxic agent Adriamycin（Adm） stimulated human breast cancer *** identified 638 genotoxic stress-elicited O-GlcNAc chromatin-associated proteins（OCPs）,including 88 O-GlcNAc chromatin-associated transcription factors and cofactors（OCTFs）,subsequently mapped their genomic loci,and constructed a comprehensive transcriptional reprograming ***,genotoxicity-induced O-GlcNAc enhances the interaction of OCPs with chromatin across the *** binding between hundreds of enhancer and promoter regions by multiple OCPs is defined as a crucial feature to specifically activate transcribe genes involved in cancer cells genotoxic stress *** identified nuclear factor erythroid 2 related factor-1（NRF1）,one of OCTFs,as a key responsive regulator in O-GlcNAc modulated cellular *** results provide a valuable clue to understand OCPs acting as a stress sensor through regulating various genes expression to protect cancer cells from genotoxic dilemma.