Key role for CTCF in establishing chromatin structure in human embryos
Key role for CTCF in establishing chromatin structure in human embryos
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CTCF 在建立人类胚胎染色质结构中的关键作用
DOI：
10.1038/s41586-019-1812-0
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发表时间：
2019-12-12
期刊：
影响因子：
64.8
通讯作者：
Chen, Zi-Jiang
中科院分区：
文献类型：
--
作者：
Chen, Xuepeng;Ke, Yuwen;Chen, Zi-Jiang
在细胞周期的间期，染色质在细胞核内以分级结构排列（1，2），其在调节基因表达方面具有重要作用（3-6）。然而，在人类胚胎发生过程中的3D染色质结构的动力学仍然未知。在这里，我们报告说，与小鼠精子不同，人类精子细胞不表达染色质调节因子CTCF，并且它们的染色质不包含拓扑相关结构域（TAD）。在人类受精后，胚胎发育过程中逐渐建立了胚胎结构。此外，A/B区室化在2细胞期的人类胚胎中消失，并在胚胎发生期间重新建立。值得注意的是，阻断合子基因组激活（ZGA）可以抑制人类胚胎中的胚胎干细胞建立，但在小鼠或果蝇中则不然。值得注意的是，CTCF在ZGA之前以非常低的水平表达，然后在ZGA阶段当观察到TAD时高度表达。CTCF敲除胚胎中的组织结构显著减少，表明人类胚胎中ZGA期间的组织结构建立需要CTCF表达。我们的研究结果表明，CTCF在人类胚胎发育过程中的三维染色质结构的建立中起着关键作用。
In the interphase of the cell cycle, chromatin is arranged in a hierarchical structure within the nucleus(1,2), which has an important role in regulating gene expression(3-6). However, the dynamics of 3D chromatin structure during human embryogenesis remains unknown. Here we report that, unlike mouse sperm, human sperm cells do not express the chromatin regulator CTCF and their chromatin does not contain topologically associating domains (TADs). Following human fertilization, TAD structure is gradually established during embryonic development. In addition, A/B compartmentalization is lost in human embryos at the 2-cell stage and is re-established during embryogenesis. Notably, blocking zygotic genome activation (ZGA) can inhibit TAD establishment in human embryos but not in mouse or Drosophila. Of note, CTCF is expressed at very low levels before ZGA, and is then highly expressed at the ZGA stage when TADs are observed. TAD organization is significantly reduced in CTCF knockdown embryos, suggesting that TAD establishment during ZGA in human embryos requires CTCF expression. Our results indicate that CTCF has a key role in the establishment of 3D chromatin structure during human embryogenesis.