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Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma
Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequen...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624633/ https://www.ncbi.nlm.nih.gov/pubmed/37648814 http://dx.doi.org/10.1038/s41375-023-02013-9 |
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author | Briest, Franziska Noerenberg, Daniel Hennch, Cornelius Yoshida, Kenichi Hablesreiter, Raphael Nimo, Jose Sasca, Daniel Kirchner, Marieluise Mansouri, Larry Inoue, Yoshikage Wiegand, Laura Staiger, Annette M. Casadei, Beatrice Korkolopoulou, Penelope Weiner, January Lopez-Guillermo, Armando Warth, Arne Schneider, Tamás Nagy, Ákos Klapper, Wolfram Hummel, Michael Kanellis, George Anagnostopoulos, Ioannis Mertins, Philipp Bullinger, Lars Rosenquist, Richard Vassilakopoulos, Theodoros P. Ott, German Ogawa, Seishi Damm, Frederik |
author_facet | Briest, Franziska Noerenberg, Daniel Hennch, Cornelius Yoshida, Kenichi Hablesreiter, Raphael Nimo, Jose Sasca, Daniel Kirchner, Marieluise Mansouri, Larry Inoue, Yoshikage Wiegand, Laura Staiger, Annette M. Casadei, Beatrice Korkolopoulou, Penelope Weiner, January Lopez-Guillermo, Armando Warth, Arne Schneider, Tamás Nagy, Ákos Klapper, Wolfram Hummel, Michael Kanellis, George Anagnostopoulos, Ioannis Mertins, Philipp Bullinger, Lars Rosenquist, Richard Vassilakopoulos, Theodoros P. Ott, German Ogawa, Seishi Damm, Frederik |
author_sort | Briest, Franziska |
collection | PubMed |
description | Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n = 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure. [Image: see text] |
format | Online Article Text |
id | pubmed-10624633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106246332023-11-05 Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma Briest, Franziska Noerenberg, Daniel Hennch, Cornelius Yoshida, Kenichi Hablesreiter, Raphael Nimo, Jose Sasca, Daniel Kirchner, Marieluise Mansouri, Larry Inoue, Yoshikage Wiegand, Laura Staiger, Annette M. Casadei, Beatrice Korkolopoulou, Penelope Weiner, January Lopez-Guillermo, Armando Warth, Arne Schneider, Tamás Nagy, Ákos Klapper, Wolfram Hummel, Michael Kanellis, George Anagnostopoulos, Ioannis Mertins, Philipp Bullinger, Lars Rosenquist, Richard Vassilakopoulos, Theodoros P. Ott, German Ogawa, Seishi Damm, Frederik Leukemia Article Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n = 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure. [Image: see text] Nature Publishing Group UK 2023-08-30 2023 /pmc/articles/PMC10624633/ /pubmed/37648814 http://dx.doi.org/10.1038/s41375-023-02013-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Briest, Franziska Noerenberg, Daniel Hennch, Cornelius Yoshida, Kenichi Hablesreiter, Raphael Nimo, Jose Sasca, Daniel Kirchner, Marieluise Mansouri, Larry Inoue, Yoshikage Wiegand, Laura Staiger, Annette M. Casadei, Beatrice Korkolopoulou, Penelope Weiner, January Lopez-Guillermo, Armando Warth, Arne Schneider, Tamás Nagy, Ákos Klapper, Wolfram Hummel, Michael Kanellis, George Anagnostopoulos, Ioannis Mertins, Philipp Bullinger, Lars Rosenquist, Richard Vassilakopoulos, Theodoros P. Ott, German Ogawa, Seishi Damm, Frederik Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma |
title | Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma |
title_full | Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma |
title_fullStr | Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma |
title_full_unstemmed | Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma |
title_short | Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma |
title_sort | frequent znf217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in b cell lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624633/ https://www.ncbi.nlm.nih.gov/pubmed/37648814 http://dx.doi.org/10.1038/s41375-023-02013-9 |
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