期刊
NATURE
卷 522, 期 7554, 页码 89-U221出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature14319
关键词
-
资金
- Rett Syndrome Research Trust
- National Institutes of Health (NIH) [1RO1NS048276]
- Damon Runyon Cancer Research Foundation [DRG-2048-10]
- William Randolf Hearst fund
- NIH [T32GM007753]
- HHMI
Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism(1). MECP2 encodes a methyl-DNA-binding protein(2) 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(3-9). 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据