Journal Article

DKFZ-2019-02150

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Glioblastoma initiating cells are sensitive to histone demethylase inhibition due to epigenetic deregulation.

Mallm, J.-P. (First author)DKFZ* ; Windisch, P.DKFZ* ; Biran, A. ; Gal, Z. ; Schumacher, S.DKFZ* ; Glass, R. ; Herold-Mende, C. ; Meshorer, E. ; Barbus, M.DKFZ* ; Rippe, K. (Last author)DKFZ*

2020
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.32649

Abstract: Tumor-initiating cells are a subpopulation of cells that have self-renewal capacity to regenerate a tumor. Here, we identify stem cell-like chromatin features in human glioblastoma initiating cells (GICs) and link them to a loss of the repressive histone H3 lysine 9 trimethylation (H3K9me3) mark. Increasing H3K9me3 levels by histone demethylase inhibition led to cell death in GICs but not in their differentiated counterparts. The induction of apoptosis was accompanied by a loss of the activating H3 lysine 9 acetylation (H3K9ac) modification and accumulation of DNA damage and downregulation of DNA damage response genes. Upon knockdown of histone demethylases KDM4C and KDM7A both differentiation and DNA damage were induced. Thus, the H3K9me3-H3K9ac equilibrium is crucial for GIC viability and represents a chromatin feature that can be exploited to specifically target this tumor subpopulation. This article is protected by copyright. All rights reserved.

Note: 2020 Mar 1;146(5):1281-1292#EA:B066#LA:B066# / #DKFZ-MOST-Ca180#

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Contributing Institute(s):

1. B066 Chromatin-Netzwerke (B066)
2. B060 Molekulare Genetik (B060)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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