Analysis of tissue-specific differentially methylated regions (TDMs) in humans
Analysis of tissue-specific differentially methylated regions (TDMs) in humans
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DOI：
10.1016/j.ygeno.2006.11.006
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发表时间：
2007-03-01
期刊：
影响因子：
4.4
通讯作者：
Nagase, Hiroki
中科院分区：
文献类型：
--
作者：
Kitamura, Eiko;Igarashi, Jun;Nagase, Hiroki
DNA甲基化的改变与哺乳动物的发育有关。因此，识别组织特异性差异甲基化区域（TDMs）对于理解其作用是必不可少的。使用限制性标记基因组扫描的6个小鼠组织，150个推定的TDM进行了鉴定，并进一步分析了14个。本研究分析了14个小鼠TDM的DNA序列。6个人类同源区域显示出对小鼠和人类的TDM，其中5个区域中的基因具有保守的组织特异性表达：在睾丸中优先表达。在9个睾丸组织中进一步分析了TDM DDX 4。启动子区域甲基化的增加与基因表达的显著降低和精子发生的缺陷显著相关，表明DDX 4启动子区域的低甲基化调节DDX 4基因在生精细胞中的表达。我们的研究结果表明，一些基因组区域的组织特异性甲基化和表达是保守的小鼠和人类之间，并建议DNA甲基化可能有重要的作用，在调节分化和组织/细胞特异性基因表达的一些基因。(c)2006年爱思唯尔公司All rights reserved.
Alterations in DNA methylation have been implicated in mammalian development. Hence, the identification of tissue-specific differentially methylated regions (TDMs) is indispensable for understanding its role. Using restriction landmark genomic scanning of six mouse tissues, 150 putative TDMs were identified and 14 were further analyzed. The DNA sequences of the 14 mouse TDMs are analyzed in this study. Six of the human homologous regions show TDMs to both mouse and human and genes in five of these regions have conserved tissue-specific expression: preferential expression in testis. A TDM, DDX4, is further analyzed in nine testis tissues. An increase in methylation of the promoter region is significantly associated with a marked reduction of the gene expression and defects in spermatogenesis, suggesting that hypomethylation of the DDX4 promoter region regulates DDX4 gene expression in spermatogenic cells. Our results indicate that some genomic regions with tissue-specific methylation and expression are conserved between mouse and human and suggest that DNA methylation may have an important role in regulating differentiation and tissue-/cell-specific gene expression of some genes. (c) 2006 Elsevier Inc. All rights reserved.