4.8 Article

Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos

Journal

NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-15607-z

Keywords

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Funding

  1. National Key RAMP
  2. D Program of China [2016YFA0100400, 2018YFC1004000, 2019YFA0110000]
  3. National Natural Science Foundation of China [31721003, 31820103009, 31771419, 31701262, 81630035, 31972882]

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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.

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Weisheng Zheng, Liping Wang, Wenteng He, Xinjie Hu, Qianshu Zhu, Liang Gu, Cizhong Jiang

Summary: Haploid embryonic stem cells (haESCs) have similar transcriptome profiles to naive pluripotent stem cells and exhibit a similar chromatin structure to embryonic stem cells (ESCs). However, haESCs lack a nucleosome depletion region found in ESCs and have different chromatin states in enhancers related to the regulation of the cell cycle. These findings suggest that haESCs have unique characteristics and mechanisms compared to differentiated cell types.

CELL PROLIFERATION (2023)

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