PXD034337

PXD034337 is an original dataset announced via ProteomeXchange.

Title	Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma (Global Proteome and PPI)
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 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.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:11:24.668.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-06 01:15:36	ID requested
⏵ 1	2024-01-26 06:11:25	announced

10.1038/s41375-023-02013-9;

Briest F, Noerenberg D, Hennch C, Yoshida K, Hablesreiter R, Nimo J, Sasca D, Kirchner M, Mansouri L, Inoue Y, Wiegand L, Staiger AM, Casadei B, Korkolopoulou P, Weiner J, Lopez-Guillermo A, Warth A, Schneider T, Nagy Á, Klapper W, Hummel M, Kanellis G, Anagnostopoulos I, Mertins P, Bullinger L, Rosenquist R, Vassilakopoulos TP, Ott G, Ogawa S, Damm F, Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma. Leukemia, 37(11):2237-2249(2023) [pubmed]

submitter keyword: ZNF217, PMBCL,Non-Hodgkin Lymphoma, genetics, precision medicine, mutation, copy-number aberration

Philipp Mertins
contact affiliation	Core Unit Proteomics, Berlin Institute of Health at Charite-Universitaetsmedizin Berlin and Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany
contact email	Philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD034337

PRIDE project URI

• PRIDE
  1. PXD034337
     1. Label: PRIDE project
     2. Name: Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma (Global Proteome and PPI)