PMID- 32909151 OWN - NLM STAT- MEDLINE DCOM- 20210921 LR - 20210921 IS - 1432-0533 (Electronic) IS - 0001-6322 (Print) IS - 0001-6322 (Linking) VI - 140 IP - 6 DP - 2020 Dec TI - C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma. PG - 951-960 LID - 10.1007/s00401-020-02225-8 [doi] AB - 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. FAU - Zhu, Jacqueline Jufen AU - Zhu JJ AD - The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. FAU - Jillette, Nathaniel AU - Jillette N AD - The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. FAU - Li, Xiao-Nan AU - Li XN AD - Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA. AD - Department of Pediatrics, Northwestern University, Chicago, IL, USA. FAU - Cheng, Albert Wu AU - Cheng AW AD - The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. albert.cheng@jax.org. AD - The Jackson Laboratory Cancer Center, Bar Harbor, ME, USA. albert.cheng@jax.org. AD - Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA. albert.cheng@jax.org. AD - Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, USA. albert.cheng@jax.org. FAU - Lau, Ching C AU - Lau CC AUID- ORCID: 0000-0001-9173-8366 AD - The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. ching.lau@jax.org. AD - The Jackson Laboratory Cancer Center, Bar Harbor, ME, USA. ching.lau@jax.org. AD - Division of Hematology-Oncology, Connecticut Children's Medical Center, Hartford, CT, USA. ching.lau@jax.org. AD - Department of Pediatrics, University of Connecticut Health Center, Farmington, CT, USA. ching.lau@jax.org. LA - eng GR - P30 CA034196/CA/NCI NIH HHS/United States GR - R01 HG009900/HG/NHGRI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200909 PL - Germany TA - Acta Neuropathol JT - Acta neuropathologica JID - 0412041 RN - 0 (C11orf95 protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Proteins) RN - 0 (RELA protein, human) RN - 0 (Transcription Factor RelA) RN - Familial ependymoma SB - IM EIN - Acta Neuropathol. 2020 Oct 23;:. PMID: 33095338 MH - Brain Neoplasms/genetics/*pathology MH - Ependymoma/*metabolism/pathology MH - Humans MH - Oncogene Proteins, Fusion/genetics MH - Proteins/*metabolism MH - Signal Transduction/physiology MH - Supratentorial Neoplasms/genetics/*pathology MH - Transcription Factor RelA/genetics/metabolism PMC - PMC7666583 OTO - NOTNLM OT - 3D genome OT - C11orf95-RELA OT - Supratentorial ependymoma OT - Transcription factor COIS- The authors declare that they have no competing interests. EDAT- 2020/09/11 06:00 MHDA- 2021/09/22 06:00 PMCR- 2020/09/09 CRDT- 2020/09/10 05:38 PHST- 2020/06/18 00:00 [received] PHST- 2020/09/02 00:00 [accepted] PHST- 2020/07/30 00:00 [revised] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/09/22 06:00 [medline] PHST- 2020/09/10 05:38 [entrez] PHST- 2020/09/09 00:00 [pmc-release] AID - 10.1007/s00401-020-02225-8 [pii] AID - 2225 [pii] AID - 10.1007/s00401-020-02225-8 [doi] PST - ppublish SO - Acta Neuropathol. 2020 Dec;140(6):951-960. doi: 10.1007/s00401-020-02225-8. Epub 2020 Sep 9.