Cargando…
C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma
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)] bu...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666583/ https://www.ncbi.nlm.nih.gov/pubmed/32909151 http://dx.doi.org/10.1007/s00401-020-02225-8 |
_version_ | 1783610159364308992 |
---|---|
author | Zhu, Jacqueline Jufen Jillette, Nathaniel Li, Xiao-Nan Cheng, Albert Wu Lau, Ching C. |
author_facet | Zhu, Jacqueline Jufen Jillette, Nathaniel Li, Xiao-Nan Cheng, Albert Wu Lau, Ching C. |
author_sort | Zhu, Jacqueline Jufen |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-020-02225-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7666583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-76665832020-11-17 C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma Zhu, Jacqueline Jufen Jillette, Nathaniel Li, Xiao-Nan Cheng, Albert Wu Lau, Ching C. Acta Neuropathol Original Paper 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-020-02225-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-09-09 2020 /pmc/articles/PMC7666583/ /pubmed/32909151 http://dx.doi.org/10.1007/s00401-020-02225-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Paper Zhu, Jacqueline Jufen Jillette, Nathaniel Li, Xiao-Nan Cheng, Albert Wu Lau, Ching C. C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma |
title | C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma |
title_full | C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma |
title_fullStr | C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma |
title_full_unstemmed | C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma |
title_short | C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma |
title_sort | c11orf95-rela reprograms 3d epigenome in supratentorial ependymoma |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666583/ https://www.ncbi.nlm.nih.gov/pubmed/32909151 http://dx.doi.org/10.1007/s00401-020-02225-8 |
work_keys_str_mv | AT zhujacquelinejufen c11orf95relareprograms3depigenomeinsupratentorialependymoma AT jillettenathaniel c11orf95relareprograms3depigenomeinsupratentorialependymoma AT lixiaonan c11orf95relareprograms3depigenomeinsupratentorialependymoma AT chengalbertwu c11orf95relareprograms3depigenomeinsupratentorialependymoma AT lauchingc c11orf95relareprograms3depigenomeinsupratentorialependymoma |