The tumor suppressor Chd5 is induced during neuronal differentiation in the developing mouse brain |
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Affiliation: | 1. Department of Pediatrics, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel;2. Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel;3. Clinical Virology Unit, Department of Clinical Microbiology & Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel;4. Pediatric Infectious Diseases Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;5. Pediatric Cardiology Department, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel;1. Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;2. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria;3. Department of Neurology, University Hospital Regensburg, Regensburg, Germany;4. Ludwig Institute for Cancer Research, Uppsala University, Box 595, BMC, 75124 Uppsala, Sweden;5. Institute of Experimental Neuroregeneration, Paracelsus Medical University, 5020 Salzburg, Austria;6. Karolinska Institute, Department of Clinical Science, Intervention and Technology (CLINTEC), K53, 14186 Stockholm, Sweden |
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Abstract: | Epigenetic regulation of gene expression orchestrates dynamic cellular processes that become perturbed in human disease. An understanding of how subversion of chromatin-mediated events leads to pathologies such as cancer and neurodevelopmental syndromes may offer better treatment options for these pathological conditions. Chromodomain Helicase DNA-binding protein 5 (CHD5) is a dosage-sensitive tumor suppressor that is inactivated in human cancers, including neural-associated malignancies such as neuroblastoma and glioma. Here we report a detailed analysis of the temporal and cell type-specific expression pattern of Chd5 in the mammalian brain. By analyzing endogenous Chd5 protein expression during mouse embryogenesis, in the neonate, and in the adult, we found that Chd5 is expressed broadly in multiple brain regions, that Chd5 sub-cellular localization undergoes a switch from the cytoplasm to the nucleus during mid-gestation, and that Chd5 expression is retained at high levels in differentiated neurons of the adult. These findings may have important implications for defining the role of CHD5-mediated chromatin dynamics in the brain and for elucidating how perturbation of these epigenetic processes leads to neuronal malignancies, neurodegenerative diseases, and neurodevelopmental syndromes. |
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Keywords: | CHD5 Cancer Gene expression Chromatin Mouse brain |
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