Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L.
Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L.
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DOI：
10.1186/1471-213x-7-104
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发表时间：
2007-09-18
影响因子：
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通讯作者：
Trasler JM
中科院分区：
文献类型：
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作者：
La Salle S;Oakes CC;Neaga OR;Bourc'his D;Bestor TH;Trasler JM
能够受精的单倍体精子的形成需要对表观遗传信息进行适当的编程。DNMT3L(DNA甲基转移酶3-like)是DNA甲基转移酶活性的调节者，在配子发生过程中如何促进DNA甲基化模式的获得仍不清楚。在此，我们报道了DNMT3L在雄性生殖细胞发育中的作用。在Dnmt3L突变小鼠模型上进行了出生后12天的发育研究；在Dnmt3L-/-雄性小鼠中观察到生殖细胞数量减少和进入减数分裂延迟，表明存在有丝分裂缺陷。一项时间表达研究表明，Dnmt3L在产前性腺细胞中的表达最高，但在精子发生过程中也被检测到并受到发育调节。应用限制性内切酶定量聚合酶链式反应(QAMP)技术，对出生后缺失DNMT3L的原始A型精原细胞进行DNA甲基化分析。与Dnmt3L+/+生殖细胞中观察到的水平相比，4号染色体和X染色体上61个位点的甲基化水平显著降低了约50%，这表明整个基因组中的许多位置都被DNMT3L标记为甲基化。更严重的是，低甲基化在GC含量较低的区域比在GC含量较高的区域更明显。综上所述，这些数据表明DNMT3L在基因组甲基化模式中发挥着比之前认为的更全球性的作用。
Formation of haploid spermatozoa capable of fertilization requires proper programming of epigenetic information. Exactly how DNMT3L (DNA methyltransferase 3-Like), a postulated regulator of DNA methyltransferase activity, contributes to DNA methylation pattern acquisition during gametogenesis remains unclear. Here we report on the role of DNMT3L in male germ cell development. A developmental study covering the first 12 days following birth was conducted on a Dnmt3L mutant mouse model; lower germ cell numbers and delayed entry into meiosis were observed in Dnmt3L-/- males, pointing to a mitotic defect. A temporal expression study showed that expression of Dnmt3L is highest in prenatal gonocytes but is also detected and developmentally regulated during spermatogenesis. Using a restriction enzyme qPCR assay (qAMP), DNA methylation analyses were conducted on postnatal primitive type A spermatogonia lacking DNMT3L. Methylation levels along 61 sites across chromosomes 4 and X decreased significantly by approximately 50% compared to the levels observed in Dnmt3L+/+ germ cells, suggesting that many loci throughout the genome are marked for methylation by DNMT3L. More so, hypomethylation was more pronounced in regions of lower GC content than in regions of higher GC content. Taken together, these data suggest that DNMT3L plays a more global role in genomic methylation patterning than previously believed.