Oncotarget

Research Papers:

The putative tumor suppressor gene EphA7 is a novel BMI-1 target

Gaëlle Prost, Sebastian Braun, Falk Hertwig, Marcus Winkler, Lucas Jagemann, Sara Nolbrant, Isabelle V. Leefa, Nils Offen, Kenichi Miharada, Stefan Lang, Isabella Artner and Ulrike A. Nuber _

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Oncotarget. 2016; 7:58203-58217. https://doi.org/10.18632/oncotarget.11279

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Abstract

Gaëlle Prost1,*, Sebastian Braun1,*, Falk Hertwig1,*, Marcus Winkler1,*, Lucas Jagemann1, Sara Nolbrant1, Isabelle V. Leefa1, Nils Offen1, Kenichi Miharada1, Stefan Lang1, Isabella Artner1, Ulrike A. Nuber1,2

1Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden

2Current address: Technical University Darmstadt, 64287 Darmstadt, Germany

*The authors contributed equally to this work

Correspondence to:

Ulrike A. Nuber, email: [email protected]

Keywords: Bmi1, EphA7, neural stem cells, DNA methylation

Received: January 28, 2016     Accepted: August 08, 2016     Published: August 13, 2016

ABSTRACT

Bmi1 was originally identified as a gene that contributes to the development of mouse lymphoma by inhibiting MYC-induced apoptosis through repression of Ink4a and Arf. It codes for the Polycomb group protein BMI-1 and acts primarily as a transcriptional repressor via chromatin modifications. Although it binds to a large number of genomic regions, the direct BMI-1 target genes described so far do not explain the full spectrum of BMI-1-mediated effects. Here we identify the putative tumor suppressor gene EphA7 as a novel direct BMI-1 target in neural cells and lymphocytes. EphA7 silencing has been reported in several different human tumor types including lymphomas, and our data suggest BMI1 overexpression as a novel mechanism leading to EphA7 inactivation via H3K27 trimethylation and DNA methylation.


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