Telomere lengthening early in development
Telomere lengthening early in development
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DOI：
10.1038/ncb1664
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发表时间：
2007-12-01
影响因子：
21.3
通讯作者：
Keefe, David L.
中科院分区：
文献类型：
--
作者：
Liu, Lin;Bailey, Susan M.;Keefe, David L.
干细胞和癌细胞主要通过端粒酶维持端粒长度（1-3）。端粒酶活性在雄性生殖系和干细胞中较高，但在成熟卵母细胞和卵裂期胚胎中较低或不存在，然后在胚泡中再次升高（3）。早期胚胎如何重置端粒长度仍然知之甚少。在这里，我们表明，卵母细胞实际上有较短的端粒比体细胞，但它们的端粒显着延长在早期卵裂发育。此外，孤雌激活的卵母细胞也延长其端粒，因此延长端粒的能力必须存在于卵母细胞本身。值得注意的是，端粒也在端粒缺失小鼠的早期卵裂胚胎中伸长，表明端粒酶不太可能是这些细胞中端粒突然伸长的原因。与端粒延长相一致，在早期卵裂胚胎中观察到广泛的端粒姐妹染色单体交换（T-SCE）和DNA重组蛋白Rad 50和TRF 1的共定位。在胚泡期胚胎中，T-SCE和DNA重组蛋白均减少，而端粒酶活性增加，端粒仅缓慢伸长。我们认为，端粒在受精后的早期卵裂周期中通过基于重组的机制延长，并且从胚泡阶段开始，端粒酶仅维持由这种替代机制建立的端粒长度。
Stem cells and cancer cells maintain telomere length mostly through telomerase(1-3). Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts(3). How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange ( T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.