Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos
Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos
复制标题
小鼠体细胞核移植胚胎中的染色质结构重组。
DOI：
10.1038/s41467-020-15607-z
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发表时间：
2020-04-14
影响因子：
16.6
通讯作者：
Cd, Shaorong Gao
中科院分区：
文献类型：
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作者：
Chen, Mo;Zhu, Qianshu;Cd, Shaorong Gao
卵母细胞质可以将体细胞核重编程为全能状态，但效率较低。体细胞核移植（SCNT）胚胎的时空染色质组织仍然难以捉摸。在这里，我们研究高阶染色质结构的小鼠SCNT胚胎使用低输入Hi-C方法。我们发现供体细胞染色质沿着典型的三维染色质结构的溶解，在SCNT后迅速转变为中期分裂相。有趣的是，基因组在激活后经历了一个类似有丝分裂中期到类似减数分裂中期II的转变。随后，弱染色质隔间和拓扑相关结构域（TADs）出现后中期退出。在逐渐重建之前，进一步去除TAD直到2细胞阶段。在SCNT胚胎中发现了明显的缺陷，包括更强的启动子边界，异常的超级增强子和启动子相互作用。这些缺陷部分由遗传性H3 K9 me 3引起，并且可以通过Kdm 4d过表达来挽救。这些观察提供了深入了解染色质结构重组过程中SCNT胚胎发育。体细胞核移植（SCNT）胚胎中染色质的组织仍然知之甚少。在这里，作者研究了小鼠SCNT胚胎的高阶染色质结构，并提供了在SCNT胚胎发育过程中染色质结构重组的见解。
The oocyte cytoplasm can reprogram the somatic cell nucleus into a totipotent state, but with low efficiency. The spatiotemporal chromatin organization of somatic cell nuclear transfer (SCNT) embryos remains elusive. Here, we examine higher order chromatin structures of mouse SCNT embryos using a low-input Hi-C method. We find that donor cell chromatin transforms to the metaphase state rapidly after SCNT along with the dissolution of typical 3D chromatin structure. Intriguingly, the genome undergoes a mitotic metaphase-like to meiosis metaphase II-like transition following activation. Subsequently, weak chromatin compartments and topologically associating domains (TADs) emerge following metaphase exit. TADs are further removed until the 2-cell stage before being progressively reestablished. Obvious defects including stronger TAD boundaries, aberrant super-enhancer and promoter interactions are found in SCNT embryos. These defects are partially caused by inherited H3K9me3, and can be rescued by Kdm4d overexpression. These observations provide insight into chromatin architecture reorganization during SCNT embryo development. The organisation of chromatin in somatic cell nuclear transfer (SCNT) embryos remains poorly understood. Here, the authors examine higher order chromatin structures of mouse SCNT embryos and provide insights into chromatin architecture reorganisation during SCNT embryo development.