C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma

AbstractSupratentorial ependymoma (ST-EPN) is a type of malignant brain tumor mainly seen in children. Since 2014, it has been known that an intrachromosomal fusionC11orf95-RELA is an oncogenic driver in ST-EPN [Parker et al. Nature 506:451 –455 (2014); Pietsch et al. Acta Neuropathol 127:609–611 (2014)] but the molecular mechanisms of oncogenesis are unclear. Here we show that the C11orf95 component of the fusion protein dictates DNA binding activity while the RELA component is required for driving the expression of ependymoma-ass ociated genes. Epigenomic characterizations using ChIP-seq and HiChIP approaches reveal that C11orf95-RELA modulates chromatin states and mediates chromatin interactions, leading to transcriptional reprogramming in ependymoma cells. Our findings provide important characterization of the molecular un derpinning ofC11orf95-RELA fusion and shed light on potential therapeutic targets forC11orf95-RELA subtype ependymoma.
Source: Acta Neuropathologica - Category: Neurology Source Type: research