The Contribution of CpG Island Methylation to the Tissue-Specific Expression of S

描述（由申请人提供）：尽管CpG岛富含可甲基化的胞嘧啶，但认为其在所有组织中均未甲基化，而与基因表达无关，除了印迹基因和位于无活性X染色体上的基因。这意味着CpG岛甲基化不能在建立和维持组织特异性基因表达中发挥作用。然而，在四种不同组织/细胞类型的初步分析中，我们鉴定了一种基因SHANK 3，其CpG岛甲基化和表达模式表现为组织类型特异性和进化保守性。我推测CpG岛甲基化有助于建立和维持SHANK 3的组织特异性表达模式。SHANK 3是正常大脑发育的必需基因，这项研究将提供一个具体的例子，说明CpG岛甲基化如何有助于组织特异性基因表达模式，并且基于我们对CpG岛的全基因组分析，可能广泛适用于数百个其他组织特异性基因。

DESCRIPTION (provided by applicant): Despite their abundance of methylatable cytosines, CpG islands are thought to be unmethylated in all tissues regardless of gene expression, except for imprinted genes and genes located on the inactive X chromosome. This implies'that CpG island methylation could not play a role in establishing and maintaining tissue-specific gene expression. However, in a preliminary analysis of four different tissue/cell types, we identified a gene, SHANK3, whose CpG island methylation and expression patterns appear tissue type- specific and evolutionarily conserved. I hypothesize that CpG island methylation helps to establish and maintain the tissue-specific expression pattern of SHANK3. This study of SHANK3, an essential gene for normal brain development, will provide a specific example of how CpG island methylation contributes to tissue-specific gene expression patterns and, based on our genome-wide analysis of CpG islands, may be widely applicable to hundreds of additional tissue-specific genes.