小柯机器人

CTCF在人类胚胎染色质结构建立中的关键作用，这一成果由山东大学陈子江团队与中科院北京基因组研究所刘江团队合作完成。该项研究成果2019年12月4日在线发表在《自然》上。

研究人员发现，与小鼠精子不同，人类精子细胞不表达染色质调节蛋白CTCF，其染色质不包含拓扑关联域（TAD）。人类受精后，TAD结构在胚胎发育过程中逐渐建立。此外，A/B区室化在2细胞阶段的人类胚胎中消失，并在胚胎发生过程中重新建立。值得注意的是，阻断合子基因组激活（ZGA）可以抑制人胚中的TAD建立，而不能抑制小鼠或果蝇中的TAD。此外，CTCF在ZGA之前以非常低的水平表达，然后在观察到TAD时在ZGA阶段高表达。TAD组织在CTCF基因敲除胚胎中显著减少，这表明ZGA在人类胚胎中建立TAD需要CTCF表达。这些结果表明，CTCF在人类胚胎发生过程中的3D染色质结构建立中具有关键作用。

据介绍，在细胞周期的中间阶段，染色质以分层结构排列在核中，这在调节基因表达方面具有重要作用。但是，人类胚胎发生过程中3D染色质结构的动态仍然未知。

附：英文原文

Title: Key role for CTCF in establishing chromatin structure in human embryos

Author: Xuepeng Chen, Yuwen Ke, Keliang Wu, Han Zhao, Yaoyu Sun, Lei Gao, Zhenbo Liu, Jingye Zhang, Wenrong Tao, Zhenzhen Hou, Hui Liu, Jiang Liu, Zi-Jiang Chen

Issue&Volume: 2019-12-04

Abstract: In the interphase of the cell cycle, chromatin is arranged in a hierarchical structure within the nucleus1,2, which has an important role in regulating gene expression36. 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. The chromatin regulator CTCF has key roles in the gradual development of hierarchical chromatin structure during human embryogenesis.

DOI: 10.1038/s41586-019-1812-0

Source:https://www.nature.com/articles/s41586-019-1812-0

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