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RNA-seq analysis for OVSAHO cells with upregulated SMARCA2 and downregulated SMARCA4 expression

ABSTRACT: The goal of this study is to explore the underlying mechanism which contributes to chemoresistance in high-grade serous carcinoma (HGSC) with low SMARCA4 and high SMARCA2 expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE212886 | GEO | 2023/02/07

REPOSITORIES: GEO

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ATAC-seq analysis for OVSAHO cells with upregulated SMARCA2 and downregulated SMARCA4 expression

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ATAC-seq analysis for OVSAHO cells with upregulated SMARCA2 and downregulated SMARCA4 expression

Project description:ATAC-seq analysis for OVSAHO cells with upregulated SMARCA2 and downregulated SMARCA4 expression

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RNA-seq analysis for OVSAHO cells with upregulated SMARCA2 and downregulated SMARCA4 expression

Project description:RNA-seq analysis for OVSAHO cells with upregulated SMARCA2 and downregulated SMARCA4 expression

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Gene expression profiling on isogenic lines expressing wild-type and mutant forms of SMARCA2 and SMARCA4

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Heterozygous mutations in SMARCA2 lead to impaired neurogenesis due to global retargeting of SMARCA4

Project description:Mammalian SWI/SNF complexes are multi-subunit chromatin remodeling complexes associated with an ATPase, either SMARCA4 or SMARCA2. Heterozygous mutations in the SMARCA2 ATPase cause Nicolaides-Baraitser Syndrome (NCBRS), an intellectual disability syndrome associated with delayed speech onset. We engineered human embryonic stem cells (hESCs) to carry NCBRS-associated heterozygous SMARCA2 K755R or R1159Q mutations. While SMARCA2 mutant hESCs were phenotypically normal, differentiation to neural progenitors cells (NPCs) was severely impaired. We find that SMARCA2 mutations cause enhancer reorganization with loss of SOX3-dependent neural enhancers and prominent emergence of astrocyte-specific de novo enhancers. Changes in chromatin accessibility at enhancers were associated with an increase in SMARCA2 binding and retargeting of SMARCA4. We show that AP-1 family member FRA2 is aberrantly overexpressed in SMARCA2 mutant NPCs, where it functions as a pioneer factor at de novo enhancers. Together, our results demonstrate SMARCA2 mutations cause impaired differentiation through enhancer reprogramming via inappropriate targeting of SMARCA4.

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