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Nature: MECP2在Rett综合征中所起作用

摘要 : 与自闭症相关的Rett综合征是由MECP2基因(该基因编码一种甲基-DNA结合蛋白)被破坏引起的,但MECP2怎样控制其他基因的转录此前仍不清楚。

 

与自闭症相关的Rett综合征是由MECP2基因(该基因编码一种甲基-DNA结合蛋白)被破坏引起的,但MECP2怎样控制其他基因的转录此前仍不清楚。现在,Michael Greenberg及同事发现,在一个小鼠模型中和在人类Rett综合征中Mecp2基因的破坏导致更长基因的优先上调,而且这些基因经常服务于神经功能。进一步的数据表明,通过“二核苷酸 CA”的“低甲基化”(hypomethylation)来降低长基因的表达,在培养出的没有MECP2的神经元中会减轻与Rett相关的功能失常。

原文链接:

Disruption of DNA-methylation-dependent long gene repression in Rett syndrome

原文摘要:

Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein2 that has been proposed to function as a transcriptional repressor, but despite numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 protein regulates transcription. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain.

来源: Nature 浏览次数:0

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