Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos

Mo Chen, Qianshu Zhu, Chong Li, Xiaochen Kou, Yanhong Zhao, Yanhe Li, Ruimin Xu, Lei Yang, Lingyue Yang, Liang Gu, Hong Wang, Xiaoyu Liu (), Cizhong Jiang () and Shaorong Gao ()
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Mo Chen: Tongji University
Qianshu Zhu: Tongji University
Chong Li: Tongji University
Xiaochen Kou: Tongji University
Yanhong Zhao: Tongji University
Yanhe Li: Tongji University
Ruimin Xu: Tongji University
Lei Yang: Tongji University
Lingyue Yang: Tongji University
Liang Gu: Tongji University
Hong Wang: Tongji University
Xiaoyu Liu: Tongji University
Cizhong Jiang: Tongji University
Shaorong Gao: Tongji University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15607-z

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