title: The putative tumor suppressor gene EphA7 is a novel BMI-1 target.
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.
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Prost
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Braun
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Falk
authors.initials: F
authors.lastname: Hertwig
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Winkler
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Lucas
authors.initials: L
authors.lastname: Jagemann
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Nolbrant
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Isabelle V
authors.initials: IV
authors.lastname: Leefa
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Offen
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Miharada
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Isabella
authors.initials: I
authors.lastname: Artner
authors.affiliation: Lund Strategic Center for Stem Cell Biology, Lund University, 22184 Lund, Sweden.|Current address: Technical University Darmstadt, 64287 Darmstadt, Germany.
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nuber
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D018929:Cell Culture Techniques / Q000379:methods; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000033:anatomy & histology / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D020547:Lateral Ventricles / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D058953:Neural Stem Cells; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D036141:Receptor, EphA7 / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: C489421:Bmi1 protein, mouse; D006657:Histones; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1; D036141:Receptor, EphA7; C581330:epha7 receptor, mouse
keywords: Bmi1; DNA methylation; EphA7; neural stem cells