Epigenetic regulation of oogenesis and germ stem cell maintenance by the Drosophila histone methyltransferase Eggless/dSetDB1.

Epigenetic regulation of oogenesis and germ stem cell maintenance by the Drosophila histone methyltransferase Eggless/dSetDB1.
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果蝇组蛋白甲基转移酶无蛋/DSETDB1对卵子发生和生殖干细胞维持的表观遗传调节。

DOI:
10.1016/j.ydbio.2014.01.014
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发表时间:
2014-04-15
影响因子:
2.7
通讯作者:
Hazelrigg T
Hazelrigg T
中科院分区:
生物学3区
文献类型:
--
作者:
Clough E;Tedeschi T;Hazelrigg T

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果蝇组蛋白赖氨酸甲基转移酶 (HKMT) Eggless (Egg/dSETDB1) 催化组蛋白 H3 赖氨酸 9 (H3K9) 的甲基化,这是抑制性异染色质的特征。我们之前的研究表明卵子发生需要 H3K9 甲基化。在这里,我们分析了一组 EMS 诱导的卵子基因突变,识别这些突变的分子损伤,并比较强功能丧失和弱等位基因对卵子发生的影响。这些研究表明卵子发生的多个阶段需要 H3K9 甲基化。嵌合表达实验表明,卵子基因并不是生殖细胞早期分化所必需的,但对于生殖细胞在卵子发生第5阶段后的存活来说是必需的。生殖干细胞的维持也需要卵子,因为卵-生殖干细胞最初可以存活,但随着雌性年龄的增长而无法维持。马赛克分析还揭示,卵子卵巢早期卵室出芽缺陷是由于卵泡干细胞及其后代对卵子的内在需求,并且卵子在生殖细胞体细胞中发挥非自主作用,影响早期生殖细胞的分化。
The Drosophila melanogaster histone lysine methyltransferase (HKMT) Eggless (Egg/dSETDB1) catalyzes methylation of Histone H3 lysine 9 (H3K9), a signature of repressive heterochromatin. Our previous studies showed that H3K9 methylation by Egg is required for oogenesis. Here we analyze a set of EMS-induced mutations in the egg gene, identify the molecular lesions of these mutations, and compare the effects on oogenesis of both strong loss-of-function and weak hypomorphic alleles. These studies show that H3K9 methylation by Egg is required for multiple stages of oogenesis. Mosaic expression experiments show that the egg gene is not required intrinsically in the germ cells for their early differentiation, but is required in the germ cells for their survival past stage 5 of oogenesis. egg is also required in germ stem cells for their maintenance, since egg− germ stem cells initially survive but are not maintained as females age. Mosaic analysis also reveals that the early egg chamber budding defects in egg− ovaries are due to an intrinsic requirement for egg in follicle stem cells and their descendents, and that egg plays a non-autonomous role in somatic cells in the germarium to influence the differentiation of early germ cells.