Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes
Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes
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DOI：
10.1073/pnas.0707442104
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发表时间：
2007-12-04
影响因子：
11.1
通讯作者：
LaSalle, Janine M.
中科院分区：
文献类型：
--
作者：
Yasui, Dag H.;Peddada, Sailaja;LaSalle, Janine M.
MECP2的突变导致自闭症谱系障碍Rett综合征。预测MeCP2结合甲基化启动子并沉默转录。然而，第一个大规模的映射26.3 Mb的印迹和非印迹基因座上的神经元MeCP2结合位点显示，59%的MeCP2结合位点的基因外，只有6%的CpG岛。MeCP2结合，CpG甲基化和基因表达的整合全基因组启动子分析显示，63%的MeCP2结合的启动子是活跃表达的，只有6%是高度甲基化的。这些结果表明MeCP2的主要功能不是甲基化启动子的沉默。
Mutations in MECP2 cause the autism-spectrum disorder Rett syndrome. MeCP2 is predicted to bind to methylated promoters and silence transcription. However, the first large-scale mapping of neuronal MeCP2-binding sites on 26.3 Mb of imprinted and non-imprinted loci revealed that 59% of MeCP2-binding sites are outside of genes and that only 6% are in CpG islands. Integrated genome-wide promoter analysis of MeCP2 binding, CpG methylation, and gene expression revealed that 63% of MeCP2-bound promoters are actively expressed and that only 6% are highly methylated. These results indicate that the primary function of MeCP2 is not the silencing of methylated promoters.