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

// Gaelle Prost 1, * , Sebastian Braun 1, * , Falk Hertwig 1, * , Marcus Winkler 1, * , Lucas Jagemann 1 , Sara Nolbrant 1 , Isabelle V. Leefa 1 , Nils Offen 1 , Kenichi Miharada 1 , Stefan Lang 1 , Isabella Artner 1 , Ulrike A. Nuber 1, 2 1 Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden 2 Current address: Technical University Darmstadt, 64287 Darmstadt, Germany * The authors contributed equally to this work Correspondence to: Ulrike A. Nuber, email: nuber@bio.tu-darmstadt.de 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.