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| Status |
Public on May 03, 2024 |
| Title |
Dynamic Chromatin Alteration Induces Oncogenic Hijacking by Essential Transcriptional Factors during Medulloblastoma Tumorigenesis [Multiome] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Using ATAC-seq analysis from GNPs to MBSHH we discovered a massive modification in chromatin accessibility during MBSHH formation. Next, using integrative bioinformatics, we identified genes of the nuclear factor I (NFI) family that function as oncogenes on the MBSHH epigenome. We demonstrate not only that these genes are essential in the early stages of murine MBSHHs tumorigenesis, but also that their genetic silencing inhibits tumor growth in murine and human MBSHHs in vitro and in vivo. Finally, we discovered that NFIA/B are post-translationally modified by an activating methylation in MBSHH, making it possibility to target this pathway. Further studies revealed that pharmacological inhibition of this methylated NFIA/B hindered tumor proliferation, demonstrating the requirement of NFIA/B for tumor progression. Collectively our data shed light on the mechanism underlying the epigenome during the formation of the most malignant pediatric brain tumor and emphasizes the importance of deciphering cancer-specific epigenome for identification of new therapeutic avenues.
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| Overall design |
Chromium Single-Cell Multiome ATAC + Gene Expression for mouse medulloblastoma GEMM model
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| Contributor(s) |
Shiraishi R, Cancila G, Kumegawa K, Maruyama R, Ayrault O, Kawauchi D |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 20, 2023 |
| Last update date |
May 04, 2024 |
| Contact name |
Kohei Kumegawa |
| E-mail(s) |
kohei.kumegawa@gmail.com
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| Organization name |
Japanese Foundation for Cancer Research
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| Street address |
3-8-31 Ariake, Koto-ku
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| City |
Tokyo |
| ZIP/Postal code |
135-8550 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE240362 |
Cancer-Specific Epigenome Identifies Oncogenic Hijacking by Nuclear Factor I Family Proteins for Medulloblastoma Progression |
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| Relations |
| BioProject |
PRJNA1019231 |
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