SMARCA4/Brg1 Coordinates Genetic and Epigenetic Networks Underlying Shh-type Medulloblastoma Development [gene expression]
Transcriptomics Dataset
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| Accession | GSE69672 |
| Title | SMARCA4/Brg1 Coordinates Genetic and Epigenetic Networks Underlying Shh-type Medulloblastoma Development [gene expression] |
| Description | 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. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69672 |
| Repository | Gene Expression Omnibus |
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