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A SOX2 engineered epigenetic silencer factor represses the glioblastoma genetic program

ABSTRACT: By rational engineering of the transcription factor SOX2, a key promoter of GBM malignancy, we generated a synthetic repressor named SOX2 Epigenetic Silencer (SES), which maintains the ability to bind to a large group of its original targets. Data from RNAseq, ATACseq, MeDIPseq, ChIPseq in GBM cells indicate that SES, through the KRAB and DNA methyltransferase 3A/L catalytic domains, epigenetically inhibits the SOX2 tumorigenic molecular network (rather than activating it as SOX2 does). This epigenetic long-term transcriptional silencing includes genes crucial for tumor maintenance and growth. Conversely, transcriptomic and epigenomic data show that SES is ineffective (thus not harmful) in healthy neural cells.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE200062 | GEO | 2022/08/10

REPOSITORIES: GEO

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