Mitotic remodeling of the replicon and chromosome structure
Mitotic remodeling of the replicon and chromosome structure
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DOI：
10.1016/j.cell.2005.08.045
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发表时间：
2005-12-02
期刊：
影响因子：
64.5
通讯作者：
Méchali, M
中科院分区：
文献类型：
--
作者：
Lemaitre, JM;Danis, E;Méchali, M
由于移植的细胞核不能支持正常的胚胎发育，通过细胞核移植实验克隆动物常常失败。我们在这里表明，有丝分裂染色体在卵背景下的形成是至关重要的适应分化的细胞核的早期发展。分化的红细胞核在爪蟾卵中复制效率低下，但如果允许先前的单个有丝分裂，则其复制速度与精子核一样快。这种有丝分裂重塑涉及拓扑异构酶II依赖性染色质环结构域的缩短和增加的复制起始因子到染色质上的招募，导致早期发育阶段的短的起点间间隔特征。它也发生在每个早期胚胎细胞周期中，并主要调节随后S期DNA复制的起始。这些结果表明，有丝分裂条件是至关重要的，以重置分化的成人供体细胞的染色质结构的胚胎DNA复制，并建议它是一个重要的步骤，在核克隆。
Animal cloning by nuclear-transfer experiments frequently fails due to the inability of transplanted nuclei to support normal embryonic development. We show here that the formation of mitotic chromosomes in the egg context is crucial for adapting differentiated nuclei for early development. Differentiated erythrocyte nuclei replicate inefficiently in Xenopus eggs but do so as rapidly as sperm nuclei if a prior single mitosis is permitted. This mitotic remodeling involves a topoisomerase II-dependent shortening of chromatin loop domains and an increased recruitment of replication initiation factors onto chromatin, leading to a short interorigin spacing characteristic of early developmental stages. It also occurs within each early embryonic cell cycle and dominantly regulates initiation of DNA replication for the subsequent S phase. These results indicate that mitotic conditioning is crucial to reset the chromatin structure of differentiated adult donor cells for embryonic DNA replication and suggest that it is an important step in nuclear cloning.