Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development.

Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development.
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DOI:
10.1016/j.ygeno.2008.09.003
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发表时间:
2009-02
期刊:
影响因子:
4.4
通讯作者:
Held, William A.
Held, William A.
中科院分区:
生物学3区
文献类型:
--
作者:
Song, Fei;Mahmood, Saleh;Ghosh, Srimoyee;Liang, Ping;Smiraglia, Domminic J.;Nagase, Hiroki;Held, William A.

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利用第二代虚拟RLGS (vRLGS)在小鼠基因组中鉴定和定位组织特异性差异甲基化区域(TDMRs)。Sequenom MassARRAY定量甲基化分析用于确认和确定组织特异性DNA甲基化差异的精细结构。tdmr具有广泛的基因内和基因间区域分布,包括CpG岛和非CpG岛区域。有些令人惊讶的是,TDMR在非启动子基因内区域的位置有很强的偏见。虽然一些tdmr在重复序列内或接近重复序列,但总体而言,它们与随机分布中预期的重复元素相关的频率较低。许多TDMRs在早期发育阶段被甲基化,但随后未甲基化,这表明主动或被动去甲基化,或未甲基化TDMRs细胞群体的扩大。在出生后的睾丸分化过程中,许多睾丸特异性TDMRs逐渐“去甲基化”。这些结果表明,发育过程中的甲基化变化是动态的,涉及去甲基化和甲基化,可能发生在胚胎发育后期甚至出生后。
Tissue specific differentially methylated regions (TDMRs) were identified and localized in the mouse genome using second generation virtual RLGS (vRLGS). Sequenom MassARRAY quantitative methylation analysis was used to confirm and determine the fine structure of tissue specific differences in DNA methylation. TDMRs have a broad distribution of locations to intragenic and intergenic regions including both CpG islands, and non-CpG islands regions. Somewhat surprising, there is a strong bias for TDMR location in non-promoter intragenic regions. Although some TDMRs are within or close to repeat sequences, overall they are less frequently associated with repetitive elements than expected from a random distribution. Many TDMRs are methylated at early developmental stages, but unmethylated later, suggesting active or passive demethylation, or expansions of populations of cells with unmethylated TDMRs. This is notable during postnatal testis differentiation where many testis-specific TDMRs become progressively “demethylated”. These results suggest that methylation changes during development are dynamic, involve demethylation and methylation, and may occur at late stages of embryonic development or even postnatally.
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