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.
Keywords:
Bmi1; DNA methylation; EphA7; neural stem cells.
MeSH terms
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Animals
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B-Lymphocytes
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Cell Culture Techniques / methods
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Cell Nucleus / metabolism
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Cell Proliferation / physiology
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Cells, Cultured
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Cerebellum / anatomy & histology
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Cerebellum / metabolism
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DNA Methylation / physiology
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Down-Regulation
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Gene Expression Regulation*
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Genes, Tumor Suppressor*
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Histones / metabolism
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Immunohistochemistry
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Ki-67 Antigen / metabolism
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Lateral Ventricles / anatomy & histology
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Lateral Ventricles / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microarray Analysis
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Neural Stem Cells
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Polycomb Repressive Complex 1 / genetics
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Polycomb Repressive Complex 1 / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Receptor, EphA7 / genetics*
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Receptor, EphA7 / metabolism
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Spleen / cytology
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Transduction, Genetic
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Up-Regulation
Substances
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Bmi1 protein, mouse
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Histones
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Ki-67 Antigen
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Proto-Oncogene Proteins
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Polycomb Repressive Complex 1
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Receptor, EphA7
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epha7 receptor, mouse