Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transitionстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 11 мая 2017 г.
Аннотация: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