The tumor suppressor Chd5 is induced during neuronal differentiation in the developing mouse brain.
The tumor suppressor Chd5 is induced during neuronal differentiation in the developing mouse brain.
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DOI：
10.1016/j.gep.2013.09.003
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发表时间：
2013-12
影响因子：
1.2
通讯作者：
Mills, Alea A.
中科院分区：
文献类型：
--
作者：
Vestin, Assaf;Mills, Alea A.
基因表达的表观遗传调控协调了在人类疾病中受到干扰的动态细胞过程。了解染色质介导事件的颠覆如何导致癌症和神经发育综合征等病理，可能为这些病理条件提供更好的治疗选择。染色体结构域解旋酶dna结合蛋白5 （CHD5）是一种剂量敏感的肿瘤抑制因子，在人类癌症中失活，包括神经相关的恶性肿瘤，如神经母细胞瘤和胶质瘤。在这里，我们报告了哺乳动物大脑中Chd5的时间和细胞类型特异性表达模式的详细分析。通过分析小鼠胚胎发生、新生儿和成人的内源性Chd5蛋白表达，我们发现Chd5在大脑多个区域广泛表达，Chd5亚细胞定位在妊娠中期经历了从细胞质到细胞核的转换，并且Chd5在成人分化神经元中保持高水平表达。这些发现可能对定义chd5介导的脑染色质动力学的作用以及阐明这些表观遗传过程的扰动如何导致神经元恶性肿瘤、神经退行性疾病和神经发育综合征具有重要意义。
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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影响因子：
37.3
作者：
Garcia I;Mayol G;Rodríguez E;Suñol M;Gershon TR;Ríos J;Cheung NK;Kieran MW;George RE;Perez-Atayde AR;Casala C;Galván P;de Torres C;Mora J;Lavarino C
通讯作者：
Lavarino C
影响因子：
64.5
作者：
Bagchi, Anindya;Papazoglu, Cristian;Mills, Alea A.
通讯作者：
Mills, Alea A.
影响因子：
3.7
作者：
Aarts, M;Dannenberg, H;de Krijger, RR
通讯作者：
de Krijger, RR
影响因子：
4.4
作者：
Kleer, CG;Bryant, BR;Merino, MJ
通讯作者：
Merino, MJ
影响因子：
6.4
作者：
Felsberg, J;Erkwoh, A;Reifenberger, G
通讯作者：
Reifenberger, G