Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state.
Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state.
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DOI：
10.1016/j.molcel.2010.01.030
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发表时间：
2010-02-26
期刊：
影响因子：
16
通讯作者：
Bird, Adrian P.
中科院分区：
文献类型：
--
作者：
Skene, Peter J.;Illingworth, Robert S.;Webb, Shaun;Kerr, Alastair R. W.;James, Keith D.;Turner, Daniel J.;Andrews, Rob;Bird, Adrian P.
MeCP2是一种核蛋白，与甲基化的DNA有亲和力，可以征集组蛋白脱乙酰基酶。MeCP2的缺乏或过量会导致严重的神经问题，这表明每个细胞的分子数量必须得到精确的调节。我们对神经元核中的MeCP2进行了量化，发现它几乎和组蛋白八聚体一样丰富。尽管有如此高的丰度，MeCP2优先与甲基化区域相关，高通量测序表明其全基因组结合跟踪甲基CpG密度。MeCP2缺乏导致神经元染色质结构的整体变化，包括组蛋白乙酰化水平升高和组蛋白H1加倍。这两种变化在胶质细胞中都检测不到，因为MeCP2在胶质细胞中的水平较低。突变的大脑还显示出重复元件转录水平的升高。我们的数据认为，MeCP2可能不是神经元中的基因特异性转录抑制因子，而是可能以DNA甲基化依赖的方式抑制全基因组的转录噪声。
MeCP2 is a nuclear protein with an affinity for methylated DNA that can recruit histone deacetylases. Deficiency or excess of MeCP2 causes severe neurological problems, suggesting that the number of molecules per cell must be precisely regulated. We quantified MeCP2 in neuronal nuclei and found that it is nearly as abundant as the histone octamer. Despite this high abundance, MeCP2 associates preferentially with methylated regions and high-throughput sequencing showed that its genome-wide binding tracks methyl-CpG density. MeCP2 deficiency results in global changes in neuronal chromatin structure, including elevated histone acetylation and a doubling of histone H1. Neither change is detectable in glia, where MeCP2 occurs at lower levels. The mutant brain also shows elevated transcription of repetitive elements. Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner.
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