title: The tumor suppressor Chd5 is induced during neuronal differentiation in the developing mouse brain.
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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Assaf
authors.initials: A
authors.lastname: Vestin
authors.forename: Alea A
authors.initials: AA
authors.lastname: Mills
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D002454:Cell Differentiation; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development; D016147:Genes, Tumor Suppressor; D051379:Mice; D058953:Neural Stem Cells / Q000201:enzymology; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology*; D009928:Organ Specificity; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D004265:DNA Helicases; C583981:Chd5 protein, mouse
keywords: CHD5; Cancer; Chromatin; Gene expression; Mouse brain