C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma

Jacqueline Jufen Zhu, Nathaniel Jillette, Xiao Nan Li, Albert Wu Cheng*, Ching C. Lau

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)951-960
Number of pages10
JournalActa Neuropathologica
Volume140
Issue number6
DOIs
StatePublished - Dec 2020

Keywords

  • 3D genome
  • C11orf95-RELA
  • Supratentorial ependymoma
  • Transcription factor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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