PLX179170

GSE100148: ATRX mutant neuroblastoma is sensitive to EZH2 inhibition via modulation of neuronal differentiation

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

We report on the characterization of ATRX in-frame fusion neuroblastoma and identify that ATRX IFF proteins re-locate from H3K9me3 enriched regions to active chromatin, such as the promoter of neural repressor REST. We further identify that REST is upregulated in ATRX IFF NB and that several neurogenesis and REST target genes are transcriptionally downregulated. Through ChIP-seq analysis, we observe that REST is bound to ATRX IFF Down genes, which have higher levels of H3K27me3. We further show that ATRX in-frame fusion neuroblastoma cells are sensitive to EZH2 inhibitors through de-repression of H3K27me3 bound neuronal function genes, includiing a subset of REST targets. SOURCE: Emily Bernstein (emily.bernstein@mssm.edu) - Bernstein Lab Mount Sinai School of Medicine