The tumor suppressor Chd5 is induced during neuronal differentiation in the developing mouse brain

肿瘤抑制因子 Chd5 在小鼠大脑发育过程中的神经元分化过程中被诱导

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作者:Assaf Vestin, Alea A Mills

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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