Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression
Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression
复制标题
DOI：
10.1073/pnas.0408436102
复制
发表时间：
2005-03-01
影响因子：
11.1
通讯作者：
Held, WA
中科院分区：
文献类型：
--
作者：
Song, F;Smith, JF;Held, WA
早期研究提出DNA甲基化可能在发育过程中调节基因表达中起作用[Riggs， A.D. (1975) Cytogenet]。细胞遗传学，14,9-25]。然而，一些关于发育过程中已知组织特异性基因DNA甲基化的研究并不支持DNA甲基化的主要作用。在这里提出的结果中，首先确定了组织特异性差异甲基化区域（tdm），然后与这些区域相关的基因表达与甲基化状态相关。限制性标记基因组扫描（RLGS）与虚拟RLGS一起用于鉴定150个tdm [Matsuyama， T., Kimura， M.T., Koike， K., Abe， T., Nakao， T., Asami， T., Ebisuzaki， T., Held， W.A, Yoshida， S. & Nagase， H. (2003) Nucleic Acids Res. 31, 4490-4496]。通过甲基化特异性PCR和硫酸氢盐基因组测序对14个tdm的分析证实，RLGS鉴定的区域以组织特异性方式差异甲基化。结果表明，5%或更多的CpG岛是tdm，这与所有CpG岛都未甲基化的一般观念存在争议。一些tdm位于基因的5'启动子CpG岛内，其表现出与甲基化状态一致的组织特异性表达模式，并在组织分化中发挥作用。
Early studies proposed that DNA methylation could have a role in regulating gene expression during development [Riggs, A.D. (1975) Cytogenet. Cell Genet. 14, 9-25]. However, some studies of DNA methylation in known tissue-specific genes during development do not support a major role for DNA methylation. In the results presented here, tissue-specific differentially methylated regions (TDMs) were first identified, and then expression of genes associated with these regions correlated with methylation status. Restriction landmark genomic scanning (RLGS) was used in conjunction with virtual RLGS to identify 150 TDMs [Matsuyama, T., Kimura, M.T., Koike, K., Abe, T., Nakao, T., Asami, T., Ebisuzaki, T., Held, W.A., Yoshida, S. & Nagase, H. (2003) Nucleic Acids Res. 31, 4490-4496]. Analysis of 14 TDMs by methylation-specific PCR and by bisulfate genomic sequencing confirms that the regions identified by RLGS are differentially methylated in a tissue-specific manner. The results indicate that 5% or more of the CpG islands are TDMs, disputing the general notion that all CpG islands are unmethylated. Some of the TDMs are within 5' promoter CpG islands of genes, which exhibit a tissue-specific expression pattern that is consistent with methylation status and a role in tissue differentiation.