Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells
Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells
复制标题
DOI：
10.1038/ncb1513
复制
发表时间：
2006-12-01
影响因子：
21.3
通讯作者：
Muegge, Kathrin
中科院分区：
文献类型：
--
作者：
De La Fuente, Rabindranath;Baumann, Claudia;Muegge, Kathrin
类疟原虫特异性解旋酶（Lsh）是一种主要的表观遗传调节因子，对哺乳动物基因组中寄生元件的DNA甲基化和转录沉默至关重要（1，2）。然而，Lsh是否参与减数分裂期间染色质介导的过程的调节尚不清楚。在这里，我们表明，LSH是必不可少的完成减数分裂和转录抑制的女性性腺中的重复元素。Lsh基因敲除小鼠的卵母细胞表现出臂间异染色质处转座因子和串联重复序列的去甲基化，以及与持续的RAD 51灶和γ H2AX磷酸化相关的不完全染色体突触。未能加载交叉相关病灶导致产生非交换染色体。观察到的严重的卵母细胞损失和缺乏卵泡形成，连同LSH核区室化在生殖系中的模式，表明LSH在雌性减数分裂期间的表观遗传基因沉默和基因组稳定性的维持中具有关键的和先前未鉴定的作用。
Lymphoid specific helicase (Lsh) is a major epigenetic regulator that is essential for DNA methylation and transcriptional silencing of parasitic elements in the mammalian genome(1,2). However, whether Lsh is involved in the regulation of chromatin-mediated processes during meiosis is not known. Here, we show that Lsh is essential for the completion of meiosis and transcriptional repression of repetitive elements in the female gonad. Oocytes from Lsh knockout mice exhibit demethylation of transposable elements and tandem repeats at pericentric heterochromatin, as well as incomplete chromosome synapsis associated with persistent RAD51 foci and gamma H2AX phosphorylation. Failure to load crossover-associated foci results in the generation of non-exchange chromosomes. The severe oocyte loss observed and lack of ovarian follicle formation, together with the patterns of Lsh nuclear compartmentalization in the germ line, demonstrate that Lsh has a critical and previously unidentified role in epigenetic gene silencing and maintenance of genomic stability during female meiosis.