Journal Article

Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition

Ulianov, Sergey V., Imakaev, Maxim, Flyamer, Ilya M., Abdennur, Nezar, Tachibana-Konwalski, Kikuë, Brandão, Hugo B., Razin, Sergey V., Gassler, Johanna, Mirny, Leonid A.

2017

Overview

Using a single-nucleus Hi-C protocol, the authors find that spatial organization of chromatin during oocyte-to-zygote transition differs between paternal and maternal nuclei within a single-cell zygote. Oocyte-to-zygote chromatin reorganization It has been difficult to investigate chromosome organization in early embryos with genomic techniques owing to the paucity of cellular material. Here, Kikuë Tachibana-Konwalski and colleagues have developed a single-nucleus Hi-C protocol, which they apply to investigate chromatin organization during the developmental transition from oocytes to zygotes in mice. They find that chromatin architecture is distinct in the paternal and maternal pronuclei within a single-cell zygote. Zygotic maternal nuclei contain topological domains and loops but no A–B compartments, whereas compartments can be observed in paternal nuclei. Clusters of contacts are variable between individual cells and do not always match topological domains across populations. The authors propose that the organization of zygotic maternal chromatin represents a transition state towards that of totipotent cells. Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism 1 . The maternal genome inherited from the oocyte and the paternal genome provided by sperm coexist as separate haploid nuclei in the zygote. How these two epigenetically distinct genomes are spatially organized is poorly understood. Existing chromosome conformation capture-based methods 2 , 3 , 4 , 5 are not applicable to oocytes and zygotes owing to a paucity of material. To study three-dimensional chromatin organization in rare cell types, we developed a single-nucleus Hi-C (high-resolution chromosome conformation capture) protocol that provides greater than tenfold more contacts per cell than the previous method 2 . Here we show that chromatin architecture is uniquely reorganized during the oocyte-to-zygote transition in mice and is distinct in paternal and maternal nuclei within single-cell zygotes. Features of genomic organization including compartments, topologically associating domains (TADs) and loops are present in individual oocytes when averaged over the genome, but the presence of each feature at a locus varies between cells. At the sub-megabase level, we observed stochastic clusters of contacts that can occur across TAD boundaries but average into TADs. Notably, we found that TADs and loops, but not compartments, are present in zygotic maternal chromatin, suggesting that these are generated by different mechanisms. Our results demonstrate that the global chromatin organization of zygote nuclei is fundamentally different from that of other interphase cells. An understanding of this zygotic chromatin ‘ground state’ could potentially provide insights into reprogramming cells to a state of totipotency.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 14/63 / 38/32 / 45/23 / 45/77 / 631/136/1455 / 631/136/2435 / 631/1647/2210/2211 / 631/337/100/101 / 631/80/386 / 64/60 / Algorithms / Animals / Biological research / Boundaries / Cell cycle / Cell Nucleus - genetics / Cell Nucleus - metabolism / Cell Transdifferentiation / Cellular Reprogramming / Chromatin / Chromatin - chemistry / Chromatin - genetics / Chromatin - metabolism / Chromosome Positioning / Chromosomes / Deoxyribonucleic acid / DNA / Female / Fertilization (Biology) / Gene expression / Genomes / Haploidy / Humanities and Social Sciences / Interphase / letter / Maternal Inheritance - genetics / Methods / Mice / multidisciplinary / Nucleic Acid Conformation / Oocytes - cytology / Oocytes - metabolism / Paternal Inheritance - genetics / Physiological aspects / Population / Science / Simulation / Single-Cell Analysis - methods / Stem cells / Stochastic Processes / Totipotent Stem Cells - cytology / Totipotent Stem Cells - metabolism / Zygote / Zygote - cytology / Zygote - metabolism