Document Type

Article

Publication Date

12-2020

Keywords

JMG, JGM, JAXCC

JAX Source

Acta Neuropathol 2020 Dec; 140(6):951-960

Volume

140

Issue

6

First Page

951

Last Page

960

ISSN

1432-0533

PMID

32909151

DOI

https://doi.org/10.1007/s00401-020-02225-8

Grant

CA034196,HG009900

Abstract

Supratentorial ependymoma (ST-EPN) is a type of malignant brain tumor mainly seen in children. Since 2014, it has been known that an intrachromosomal fusion C11orf95-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-associated 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 underpinning of C11orf95-RELA fusion and shed light on potential therapeutic targets for C11orf95-RELA subtype ependymoma.

Comments

We would like to thank members of the CCL laboratory at the Jackson Laboratory for Genomic Medicine for helpful discussions and Amanda Lazarus for administrative support.

This article is licensed under a Creative Commons Attribution 4.0 International License.

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