A unique configuration of genome-wide DNA methylation patterns in the testis
A unique configuration of genome-wide DNA methylation patterns in the testis
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DOI：
10.1073/pnas.0607521104
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发表时间：
2007-01-02
影响因子：
11.1
通讯作者：
Trasler, J. M.
中科院分区：
文献类型：
--
作者：
Oakes, C. C.;La Salle, S.;Trasler, J. M.
在哺乳动物的生命周期中，全基因组表观遗传重编程的两个阶段是在体细胞模式确立的早期胚胎和生殖细胞发育期间。尽管体细胞和生殖细胞的重新编程状态之间有一些差异，但基因组甲基化的总体模式被认为是相似的。利用限制性地标基因组扫描检测随机分布在整个基因组中的大约2,600个基因座，我们发现睾丸DNA的甲基化状态非常明显，显示出相对于体细胞组织8倍的低甲基化基因座数量。对>；300基因座的鉴定和分析表明，这些区域通常位于远离基因CpG岛和5‘区的非重复序列中。我们发现，造成这些差异的一个因素是，非CpG岛DNA的甲基化状态与染色体内GC含量的区域水平相关，并且这种关系在睾丸和体细胞组织之间是反向的。我们还表明，在Dnmt3L缺陷小鼠中，这种独特的睾丸DNA甲基化模式尚未建立，这些小鼠表现出与生殖细胞染色体结构异常相关的不育。睾丸DNA的这些特殊性质表明了一种广泛的、独特的表观遗传状态，这可能与维持男性生殖细胞独特的染色体结构有关。
In the mammalian lifecycle, the two periods of genome-wide epigenetic reprogramming are in the early embryo, when somatic patterns are set, and during germ cell development. Although some differences between the reprogrammed states of somatic and germ cells have been reported, overall patterns of genomic methylation are considered to be similar. Using restriction landmark genomic scanning to examine approximate to 2,600 loci distributed randomly throughout the genome, we find that the methylation status of testicular DNA is highly distinct, displaying eightfold the number of hypomethylated loci relative to somatic tissues. Identification and analysis of > 300 loci show that these regions are generally located within nonrepetitive sequences that are away from CpG islands and 5' regions of genes. We show that a contributing factor for these differences is that the methylation state of non-CpG-island DNA is correlated with the regional level of GC content within chromosomes and that this relationship is inverted between the testis and somatic tissues. We also show that in Dnmt3L-deficient mice, which exhibit infertility associated with abnormal chromosomal structures in germ cells, this unique testicular DNA methylation pattern is not established. These special properties of testicular DNA point to a broad, distinct epigenetic state that may be involved in maintaining a unique chromosomal structure in male germ cells.