Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition
By Ilya M. Flyamer, Johanna Gassler, Maxim Imakaev, Hugo B. Brandão, Sergey V. Ulianov, Nezar Abdennur, Sergey V. Razin, Leonid A. Mirny, Kikuë Tachibana-Konwalski. Nature, 2017
693 citations recorded by the source corpus.
Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism. 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 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. 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.
Subfields: Molecular Biology, Plant Science
View Paper: https://www.semanticscholar.org/paper/d82441dde46eac6233dcd0626b355de2570fb6f4
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In Molecular Biology
Citations in the corpus
- Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells (2018, background): “An alternative view has thus been proposed that the genome is not packaged into spatially segregated domain structures in single cells but is largely organized by recurrent pairwise interactions in an otherwise diverse ensemble of conformational configurations, with TADs being considered an emergent”
- Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III (2020, background): “Also, the chromatin organizations of transcriptionally inactive mature oocytes and sperms are quite similar to the embryonic stem cells [17, 19-21], implicating that it might not be transcription per se, but transcription-associated proteins contribute to the 3D genome organization.”
- Gene regulatory network inference in the era of single-cell multi-omics (2023, background): “Despite some high-throughput alternatives 167,168 , chromosome conformation capture techniques pose new challenges owing to their sparse nature 169 and the facts that they still require integration with other modalities and their protocol can be hard to reproduce 170,171 .”
- Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins (2017, neutral): “In support of this idea, it has been proposed based on single-nucleus Hi-C experiments that TADs emerge from averaging interactions in large cell populations (Flyamer et al, 2017).”