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| Status |
Public on Jun 21, 2021 |
| Title |
An integrated epigenome and transcriptome analysis to clarify the effect of epigenetic inhibitors in gastrointestinal stromal cells (ChIP-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epigenetic alterations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). To obtain better insight into the GIST epigenome, we analyzed genome-wide histone modification and DNA methylation in GIST cells. Trimethylation of histone H3 lysine 3 (H3K4me3), DNA methylome, and transcriptome in GIST-T1 cells were analyzed by chromatin immunoprecipitation-sequencing (ChIP-seq), Infinium HumanMethylation450 BeacChip, and gene expression microarray. Enrichment of H3K4me3 at transcription start sites (TSSs) is positively correlated with gene expression, while DNA methylation is negatively associated with gene expression in GIST-T1 cells. We found that treatment with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor not only upregulated genes with DNA methylation, but also activated a number of interferon signaling-related genes. ChIP-seq analysis revealed that the drug treatment significantly upregulated H3K4me3 levels at TSS regions as well as retrotransposons including endogenous retroviruses (ERVs). Finally, by utilizing the omics data, we screened epigenetically silenced long non-coding RNA genes, and found that hypermethylation of MEG3 is a frequent event and an indicator of worse outcome in GIST patients. Our data suggest that epigenetic inhibitors may activate interferon signaling via viral mimicry in GIST cells. We also show that epigenome data obtained in this study could be a useful resource to identify novel GIST-related genes.
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| Overall design |
GIST-T1 cells were treated with 2 μM 5-aza-2’-deoxycytidine (5-aza-dC; Sigma-Aldrich) for 72 hours and then treated with or without 3 mM 4-phenylbutyric acid (4-PBA; Sigma-Aldrich) for an additional 48 hour, replacing drug and medium every 24 hours.
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| Contributor(s) |
Niinuma T, Suzuki H |
| Citation(s) |
34083271 |
| Submission date |
Apr 05, 2021 |
| Last update date |
Jun 24, 2021 |
| Contact name |
Hiromu Suzuki |
| E-mail(s) |
hsuzuki@sapmed.ac.jp
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| Phone |
+81-11-611-2111
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| Organization name |
Sapporo Medical University
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| Department |
Department of Molecular Biology
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| Street address |
S1, W17, Chuo-ku
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| City |
Sapporo |
| State/province |
Hokkaido |
| ZIP/Postal code |
060-8556 |
| Country |
Japan |
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| Platforms (1) |
| GPL13393 |
AB SOLiD 4 System (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE171499 |
An integrated epigenome and transcriptome analysis to clarify the effect of epigenetic inhibitors in gastrointestinal stromal cells |
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| Relations |
| BioProject |
PRJNA719812 |
| SRA |
SRP313534 |
