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Status |
Public on Dec 10, 2020 |
Title |
O-GlcNAc regulates MTA1 transcriptional activity during breast cancer cells genotoxic adaptation |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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.
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Overall design |
MTA1 ChIP-seq was performed in HA-MTA1-WT and HA-MTA1-3A expressed MCF-7 cells using anti-HA magnetic beads. Gene expression profiling of HA-MTA1-WT and HA-MTA1-3A expressed MCF-7 cells were performed by RNA-seq.
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Contributor(s) |
Xie X, Wu Q, Zhang K, Liu Y, Zhang N, Chen Q, Wang L, Li W, Zhang J, Liu Y |
Citation missing |
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Submission date |
Dec 09, 2020 |
Last update date |
Dec 12, 2020 |
Contact name |
bo yu liu |
E-mail(s) |
liuyubo@dlut.edu.cn
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Phone |
15842607600
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Organization name |
Dalian University of Technology
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Street address |
Dagong Road 2
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City |
panjin |
State/province |
liaoning |
ZIP/Postal code |
124000 |
Country |
China |
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Platforms (1) |
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Samples (10)
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Relations |
BioProject |
PRJNA683874 |
SRA |
SRP297403 |