Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition.
Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition.
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DOI：
10.1038/nature21711
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发表时间：
2017-04-06
期刊：
影响因子：
64.8
通讯作者：
Tachibana-Konwalski K
中科院分区：
文献类型：
--
作者：
Flyamer IM;Gassler J;Imakaev M;Brandão HB;Ulianov SV;Abdennur N;Razin SV;Mirny LA;Tachibana-Konwalski K
染色质在受精后被重新编程，以产生具有产生新生物体潜力的全能性受精卵。通过卵母细胞遗传的母系基因组和由精子提供的父系基因组作为单独的单倍体核共存于受精卵中。这两种表观遗传上不同的基因组是如何在空间上组织的，人们知之甚少。由于材料的缺乏，现有的基于染色体构象捕获的方法不适用于卵母细胞和受精卵。为了研究罕见细胞类型中的三维染色质组织，我们开发了一种单核Hi-C （snHi-C）协议，该协议提供的每个细胞的接触量比以前的方法多10倍。在这里，我们发现在小鼠卵细胞向受精卵的转变过程中，染色质结构是独特的重组，并且在单细胞受精卵的父系核和母系核中是不同的。基因组组织的特征包括室，拓扑相关结构域（tad）和环存在于单个卵母细胞中，当在基因组上平均时；基因座上的每个特征在细胞之间都是可变的。在亚兆基水平上，我们观察到违反TAD边界但平均为TAD的随机接触簇。引人注目的是，我们发现TADs和环而不是室室存在于合子母染色质中，这表明它们是由不同的机制产生的。我们的研究结果表明，合子细胞核的整体染色质组织与其他间期细胞有根本的不同。对这种合子染色质“基态”的理解有可能提供对全能性重编程的见解。
Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism. The maternal genome inherited through 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 inapplicable to oocytes and zygotes due to a paucity of material. To study the 3D chromatin organization in rare cell types, we developed a single-nucleus Hi-C (snHi-C) protocol that provides >10-fold more contacts per cell than the previous method. Here we show that chromatin architecture is uniquely reorganized during the mouse oocyte-to-zygote transition 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; each feature at a locus is variable between cells. At the sub-megabase level, we observe stochastic clusters of contacts that violate TAD boundaries but average into TADs. Strikingly, 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 other interphase cells. An understanding of this zygotic chromatin “ground state” has the potential to provide insights into reprogramming to totipotency.
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影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
48
作者：
Ramani V;Deng X;Qiu R;Gunderson KL;Steemers FJ;Disteche CM;Noble WS;Duan Z;Shendure J
通讯作者：
Shendure J
影响因子：
5.6
作者：
Barutcu AR;Fritz AJ;Zaidi SK;van Wijnen AJ;Lian JB;Stein JL;Nickerson JA;Imbalzano AN;Stein GS
通讯作者：
Stein GS
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B