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Nature. 2017 Jul 12;547(7662):232-235. doi: 10.1038/nature23263.

Allelic reprogramming of 3D chromatin architecture during early mammalian development.

Author information

1
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
2
PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
3
Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China.
4
Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing 100084, China.
5
MOE Key Laboratory of Bioinformatics; Bioinformatics Division, TNLIST; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China.
6
Department of Biological Sciences, Center for Systems Biology, The University of Texas, Dallas 800 West Campbell Road, RL11 Richardson, Texas 75080-3021, USA.
7
The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Abstract

In mammals, chromatin organization undergoes drastic reprogramming after fertilization. However, the three-dimensional structure of chromatin and its reprogramming in preimplantation development remain poorly understood. Here, by developing a low-input Hi-C (genome-wide chromosome conformation capture) approach, we examined the reprogramming of chromatin organization during early development in mice. We found that oocytes in metaphase II show homogeneous chromatin folding that lacks detectable topologically associating domains (TADs) and chromatin compartments. Strikingly, chromatin shows greatly diminished higher-order structure after fertilization. Unexpectedly, the subsequent establishment of chromatin organization is a prolonged process that extends through preimplantation development, as characterized by slow consolidation of TADs and segregation of chromatin compartments. The two sets of parental chromosomes are spatially separated from each other and display distinct compartmentalization in zygotes. Such allele separation and allelic compartmentalization can be found as late as the 8-cell stage. Finally, we show that chromatin compaction in preimplantation embryos can partially proceed in the absence of zygotic transcription and is a multi-level hierarchical process. Taken together, our data suggest that chromatin may exist in a markedly relaxed state after fertilization, followed by progressive maturation of higher-order chromatin architecture during early development.

PMID:
28703188
DOI:
10.1038/nature23263
[Indexed for MEDLINE]

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