Chromatin dynamics during epigenetic reprogramming in the mouse germ line.
Chromatin dynamics during epigenetic reprogramming in the mouse germ line.
复制标题
DOI：
10.1038/nature06714
复制
发表时间：
2008-04-17
期刊：
影响因子：
64.8
通讯作者：
Surani, M. Azim
中科院分区：
文献类型：
--
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
生殖细胞谱系表现出独特的特征，这对于产生全能性至关重要。在这个谱系中的独特事件是DNA去甲基化和消除父母的印记，这发生在胚胎第11.5天（E11.5）后，原始生殖细胞（PGCs）已经进入发育中的性腺。关于所涉及的机制还知之甚少，除了这似乎是一个活跃的过程。在这里，我们检查了染色质中的相关变化，以进一步了解这种重编程事件。我们发现，在这个过程中，染色质的变化发生在两个步骤。在E8.5时在新生PGC中观察到的第一个变化建立了具有与多能性相关的一些特征的独特染色质签名。随后，在E11.5，当这些PGC驻留在性腺中时，核结构发生重大变化，伴随着几个组蛋白修饰标记的广泛擦除以及组蛋白变体的交换沿着。此外，此时，与组蛋白交换有关的组蛋白伴侣蛋白HIRA和NAP1显示在经历重编程的PGC核中积累。因此，我们认为组蛋白替换的机制是这些染色质重排发生的关键。我们在这里展示的显着的染色质变化与全基因组DNA去甲基化过程密切相关。基于所观察到的事件的时间，我们提出，如果DNA去甲基化需要基于DNA修复的机制，那么明显的组蛋白替换将不是先决条件，而是代表修复诱导的反应事件。
The germ cell lineage exhibits unique characteristics, which are essential towards generating totipotency. Among the distinctive events in this lineage is DNA demethylation and the erasure of parental imprints, which occur on embryonic day 11.5 (E11.5) after the primordial germ cells (PGCs) have entered into the developing gonads . Little is yet known about the mechanism involved, except that this appears to be an active process. Here we have examined the associated changes in the chromatin to gain further insights into this reprogramming event. We show that chromatin changes during this process occur in two-steps. The first changes observed in nascent PGCs at E8.5 establish a distinctive chromatin signature with some characteristics associated with pluripotency. Subsequently, at E11.5 when these PGCs are residing in the gonads, major changes occur in nuclear architecture with an extensive erasure of several histone modification marks along with exchange of histone variants. Furthermore, at this time, the histone chaperones, HIRA and NAP1, which are implicated in histone exchange, show accumulation in PGC nuclei undergoing reprogramming. We thus suggest that the mechanism of histone replacement is critical for these chromatin rearrangements to occur. The striking chromatin changes we show here are intimately linked with the process of genome-wide DNA demethylation. Based on the timing of the observed events, we propose, that if DNA demethylation entails DNA repair based mechanism, the evident histone replacement would rather than being a prerequisite, represent a repair-induced response event.
登录
查看更多内容
影响因子：
4.8
作者：
Kepert, JF;Mazurkiewicz, J;Rippe, K
通讯作者：
Rippe, K
影响因子：
21.3
作者：
Ancelin, Katia;Lange, Ulrike C.;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
4.8
作者：
Park, YJ;Chodaparambil, JV;Luger, K
通讯作者：
Luger, K
影响因子：
11.4
作者：
Walfridsson, Julian;Khorosjutina, Olga;Ekwall, Karl
通讯作者：
Ekwall, Karl
影响因子：
--
作者：
Zweidler, A
通讯作者：
Zweidler, A