Oakes C C, La Salle S, Smiraglia D J, Robaire B, Trasler J M
Department of Pharmacology and Therapeutics, Human Genetics, McGill University, Montreal, QC, Canada.
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):228-33. doi: 10.1073/pnas.0607521104. Epub 2006 Dec 26.
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 approximately 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.
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时期分别是在早期胚胎中（此时体细胞模式被设定）以及生殖细胞发育期间。尽管已经报道了体细胞和生殖细胞重编程状态之间的一些差异，但基因组甲基化的总体模式被认为是相似的。我们使用限制性内切酶标记基因组扫描来检测随机分布于整个基因组中的约2600个位点，发现睾丸DNA的甲基化状态高度不同，相对于体细胞组织，其低甲基化位点的数量是体细胞组织的八倍。对300多个位点的鉴定和分析表明，这些区域通常位于远离CpG岛和基因5'区域的非重复序列内。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相反的。我们还表明，在Dnmt3L基因缺陷的小鼠中（这些小鼠表现出与生殖细胞中异常染色体结构相关的不育症），这种独特的睾丸DNA甲基化模式并未建立。睾丸DNA的这些特殊性质表明存在一种广泛的、独特的表观遗传状态，可能参与维持雄性生殖细胞中独特的染色体结构。
