Dataset Information

Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma (Global Proteome and PPI)

ABSTRACT: 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 an activated B cell phenotype. 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Blood

DISEASE(S): Lymphoma

SUBMITTER: Marieluise Kirchner

LAB HEAD: Philipp Mertins

PROVIDER: PXD034337 | Pride | 2024-01-26

REPOSITORIES: Pride

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			Action	DRS
	Statler_20191004_SN_HStmt_Briest_F01.raw	Raw
	Statler_20191004_SN_HStmt_Briest_F02.raw	Raw
	Statler_20191004_SN_HStmt_Briest_F03.raw	Raw
	Statler_20191004_SN_HStmt_Briest_F04.raw	Raw
	Statler_20191004_SN_HStmt_Briest_F05.raw	Raw

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Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma.

Briest Franziska F Noerenberg Daniel D Hennch Cornelius C Yoshida Kenichi K Hablesreiter Raphael R Nimo Jose J Sasca Daniel D Kirchner Marieluise M Mansouri Larry L Inoue Yoshikage Y Wiegand Laura L Staiger Annette M AM Casadei Beatrice B Korkolopoulou Penelope P Weiner January J Lopez-Guillermo Armando A Warth Arne A Schneider Tamás T Nagy Ákos Á Klapper Wolfram W Hummel Michael M Kanellis George G Anagnostopoulos Ioannis I Mertins Philipp P Bullinger Lars L Rosenquist Richard R Vassilakopoulos Theodoros P TP Ott German G Ogawa Seishi S Damm Frederik F

Leukemia 20230830 11

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- ...[more]

PMID: 37648814

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