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Chromatin bound O-GlcNAc proteins related to stress response and transcriptional regulation.

ABSTRACT: O-GlcNAcylation performs a critical role in regulating stress response program and cellular homeostasis. However, systematic studies of O-GlcNAc regulated genotoxic stress-responsive transcriptional reprograming have been limited. The GalNAz metabolic labeled global chromatin-associated proteins were isolated from the cross-linked MCF-7 and MCF-7/ADR cells nucleus, and then modified by downstream click-chemistry. The de-crosslinked O-GlcNAz chromatin-bound proteins were enriched for label-free quantitative proteomics by LC-MS/MS.

ORGANISM(S): Homo Sapiens

SUBMITTER: yubo liu

PROVIDER: PXD016713 | iProX | Sun Aug 30 00:00:00 BST 2020

REPOSITORIES: iProX

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

Liu Yubo Y Chen Qiushi Q Zhang Nana N Zhang Keren K Dou Tongyi T Cao Yu Y Liu Yimin Y Li Kun K Hao Xinya X Xie Xueqin X Li Wenli W Ren Yan Y Zhang Jianing J

Nature communications 20201119 1

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 c ...[more]

PMID: 33214551

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Genome-wide maps of O-GlcNAc proteins in human breast cancer cells by next generation sequencing

Project description:We applied the chemical reporter-based metabolic labeling method to acquire O-GlcNAc modified proteins chromatin loci. Human breast cancer cell line MCF-7, as well as the genotoxic stress (Adriamycin) adapted cells MCF-7/ADR, were fed with 1 mM GalNAz. Metabolic labeled O-GlcNAz chromatin were crosslinked, sonicated and enriched by bioorthogonal chemistry. Then, the genomic DNA fragments bounded by O-GlcNAc mark were de-crosslinked, and constructed into libraries following by next-generation sequencing (Chemoselective O-GlcNAc chromatin sequencing, COGC-seq). To verify the robustness of this chemical reporter-based metabolic labeling method, we compared the results in MCF-7 and MCF-7/ADR cells with classical lectin succinylated wheat germ agglutinin (sWGA) ChIP-seq strategy. We also analyzed gene expression MCF-7 and MCF-7/ADR cells by RNA-seq.

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Project description:Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Acting in multimeric protein complexes, these factors control structure and function of chromatin. We used a robust affinity purification mass spectrometry (AP-MS) approach to systematically map the PcG protein interactome in a single human cell line. Importantly, we uncovered the topology map of the human PR-DUB de-ubiquitination complexes, which comprise the O-linked N-acetylglucosamine transferase OGT1 and a number of transcription factors. Here we provide genome-wide chromatin maps of identified PR-DUB1 subunits ASXL1, FOXK1 and the OGT1 catalyzed modification O-GlcNAc based on ChIP-seq. Our data set comprises 3 ChIP-seq samples plus 2 input control samples using chromatin from Flp-In HEK293 T-REx cells cells which was immunoprecipitated using antibodies against ASXL1, FOXK1 and O-GlcNAc.

2016-09-08 | E-GEOD-51673 | biostudies-arrayexpress

Chemoproteomic profiling of O-GlcNAcylated proteins and identification of O-GlcNAc transferases in rice

Project description:O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modiﬁcation occurring in both animals and plants. Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. Furthermore, we discovered two O-GlcNAc transferases (OsOGTs) in rice. By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants.

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O-GlcNAc regulates MTA1 transcriptional activity during breast cancer cells genotoxic adaptation

Project description:Chromatin modifier metastatic tumor protein 1 (MTA1), closely correlated with the development and progression in breast cancer, has a fantastic role in multiple cellular processes, including gene expression and cell homeostasis. Although MTA1 is a stress-responsive gene, its role in genotoxic adaptation remains unexplored. Here, we demonstrate that O-GlcNAc modification promotes MTA1 to interact with chromatin and regulates target gene expression, contributing to breast cancer cell genotoxic adaptation. MTA1 is modified with O-GlcNAc residues at serine 237/241/246 in adriamycin adaptive breast cancer cells and that modification improves the genome-wide interactions of MTA1 with gene promotor regions by enhancing its association with nucleosome remodeling and histone deacetylation (NuRD) complex. Further, O-GlcNAc-modulated MTA1 chromatin-binding influences the specific transcriptional regulation of genes involved in the adaptation of breast cancer cells to genotoxic stress. We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-HA magnetic beads in HA-MTA1-WT or HA-MTA1-3A stably expressed MCF-7 cells. Next-generation sequencing libraries were generated and amplified for 15 cycles with BGISEQ kit. 100-300 bp DNA fragments were gel-purified and sequenced with BGISEQ-500 (BGI). Two biological replicates of the ChIP-seq were performed. We also analyzed gene expression in MTA1-WT and MTA1-3A expressed cells by RNA-seq.

2020-12-10 | GSE162932 | GEO

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