|
| Status |
Public on Sep 14, 2016 |
| Title |
SMARCA4/Brg1 Coordinates Genetic and Epigenetic Networks Underlying Shh-type Medulloblastoma Development [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Medulloblastoma could be classified into four subtypes: Wnt, Shh, Group 3, and Group 4. Subtypes of medulloblastoma have distinct epigenetic properties. We report that a chromatin regulator SMARCA4/Brg1 controls a transcriptional program that specifically required for Shh-type medulloblastoma identity and proliferation. We show that Brg1 deletion significantly inhibited tumor formation and progression in a mouse medulloblastoma model. Genomic experiments indicate that Brg1 specifically coordinates with key transcription factors including Gli1, Atoh1, and REST to regulate the expression of both oncogenes and tumor suppressors. Shh-type medulloblastoma displays distinct H3K27me3 properties. We demonstrate that Brg1 modulates activities of H3K27me3 modifiers to regulate expression of medulloblastoma genes. Brg1 is important for the growth of a human medulloblastoma cell line and Brg1-regulated pathways are conserved in human Shh-type medulloblastoma. This study reveals a novel epigenetic mechanism that controls medulloblastoma development and provides a rationale for developing subtype-specific treatment strategies.
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| |
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| Overall design |
ChIP-seq analysis of Brg1 binding in SmoM2 medulloblastoma.
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| |
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| Contributor(s) |
Shi X, Xuan Z, Wu J |
| Citation(s) |
27065321 |
| Submission date |
Jun 08, 2015 |
| Last update date |
Dec 23, 2022 |
| Contact name |
Zhenyu Xuan |
| E-mail(s) |
zhenyu.xuan@utdallas.edu
|
| Phone |
972-883-2518
|
| Organization name |
UT Dallas
|
| Street address |
800 West Campbell
|
| City |
Richardson |
| State/province |
TX |
| ZIP/Postal code |
75080 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE69674 |
SMARCA4/Brg1 Coordinates Genetic and Epigenetic Networks Underlying Shh-type Medulloblastoma Development |
|
| Relations |
| BioProject |
PRJNA286140 |
| SRA |
SRP059254 |
