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Nature:干细胞中的稳定表观遗传记忆

摘要 : 以色列魏茨曼科学研究所的研究人员建立一种方法来估计DNA甲基化周转率,发现胚胎干细胞能够在没有甲基化的克隆传输的情况下维持一个稳定的表观遗传状态。相关文章发表于2014年7月13日的《Nature》杂志上。
图示:周转率的验证过程

图示:周转率的验证过程

DNA甲基化等表观遗传机制帮助基因调控程序的稳定维持。

在这项研究中,Amos Tanay及同事建立了用来估计DNA甲基化周转率的一个方法,发现胚胎干细胞能够在没有甲基化的克隆传输的情况下维持一个稳定的表观遗传状态。

相比之下,体细胞会向后代传输相当多的表观遗传信息,但这使得体细胞表观基因组更容易受噪音影响。

原文摘要:

Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells

Zohar Shipony, Zohar Mukamel, Netta Mendelson Cohen, Gilad Landan, Elad Chomsky,Shlomit Reich Zeliger, Yael Chagit Fried, Elena Ainbinder, Nir Friedman & Amos Tanay

 Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-specific gene expression. Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. In contrast, somatic cells transmit considerable epigenetic information to progenies. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epimutations can accumulate to massively perturb the epigenomic ground state. The rate of epigenetic perturbation depends on the genomic context, and, in particular, DNA methylation loss is coupled to late DNA replication dynamics. Epigenetic perturbation is not observed in the pluripotent state, because the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the epigenome can be reprogrammed quickly and to near perfection after induced pluripotency.

对应Nature杂志: 2014年9月4日Nature杂志精选

来源: Nature 浏览次数:129

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