Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3
Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3
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DOI：
10.1038/ng1563
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发表时间：
2005-06-01
期刊：
影响因子：
30.8
通讯作者：
Costello, JF
中科院分区：
文献类型：
--
作者：
Ching, TT;Maunakea, AK;Costello, JF
CpG 岛存在于所有人类和小鼠基因的一半中，并且通常与启动子或外显子重叠。我们开发了一种使用 BAC 克隆阵列和甲基化敏感限制酶 NotI 来高分辨率分析全基因组 CpG 岛甲基化状态的方法。在这里，我们证明了该方法的准确性和特异性。通过计算绘制所有 NotI 位点的图谱，可以在整个基因组中以单核苷酸精度定义甲基化事件。我们还证明了使用不同的甲基化敏感限制性酶 BssHII 的阵列方法的独特可扩展性。我们鉴定并验证了在正常人体组织中以组织特异性方式甲基化的新 CpG 岛位点。 CpG 岛的甲基化状态与多个基因的基因表达相关，其中包括 SHANK3，它编码神经元突触后密度中的结构蛋白。 SHANK3 的缺陷似乎是人类 22q13 缺失综合征的根源。此外，SHANK3 的这些模式在小鼠和大鼠中是保守的。
CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.