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Allelic reprogramming of 3D chromatin architecture during early mammalian development

机译：哺乳动物早期发育过程中3D染色质结构的等位基因重编程

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摘要

In mammals, chromatin organization undergoes drastic reprogramming after fertilization(1). 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.
机译：在哺乳动物中，染色质组织受精后会发生剧烈的重编程（1）。然而，染色质的三维结构及其在植入前发育中的重新编程仍然知之甚少。在这里，通过开发低输入的Hi-C（全基因组染色体构象捕获）方法，我们检查了小鼠早期发育过程中染色质组织的重编程。我们发现卵母细胞在中期II显示均匀染色质折叠，缺乏可检测的拓扑关联域（TADs）和染色质区室。引人注目的是，染色质受精后显示出大大降低的高级结构。出乎意料的是，染色质组织的后续建立是一个延长的过程，贯穿整个植入前的发展，其特征在于TAD的缓慢整合和染色质区室的分离。两组亲代染色体在空间上彼此分离，并在受精卵中显示出明显的区室化。这种等位基因分离和等位基因区室化可以发现到8细胞阶段。最后，我们表明，在没有合子转录的情况下，植入前胚胎中的染色质紧缩可以部分进行，并且是一个多层次的分层过程。综上所述，我们的数据表明，染色质受精后可能以明显的松弛状态存在，随后在早期发育过程中逐步成熟了高级染色质结构。

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  • 来源
    《Nature》 |2017年第7662期|232-235|共4页
  • 作者

    Du Zhenhai; Zheng Hui; Huang Bo; Ma Rui; Wu Jingyi; Zhang Xianglin; He Jing; Xiang Yunlong; Wang Qiujun; Li Yuanyuan; Ma Jing; Zhang Xu; Zhang Ke; Wang Yang; Zhang Michael Q.; Gao Juntao; Dixon Jesse R.; Wang Xiaowo; Zeng Jianyang; Xie Wei;

  • 作者单位

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Peking Univ, Acad Adv Interdisciplinary Studies, PKU THU Ctr Life Sci, Beijing 100871, Peoples R China;

    Tsinghua Univ, Inst Interdisciplinary Informat Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Sch Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100084, Peoples R China;

    Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China|Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China|Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China|Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China|Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China|Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China|Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China;

    Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China|Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China|Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China;

    Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China|Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China|Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China|Univ Texas Dallas, Ctr Syst Biol, Dept Biol Sci, 800 West Campbell Rd,RL11, Richardson, TX 75080 USA;

    Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;

    Tsinghua Univ, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China|Tsinghua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China|Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China;

    Tsinghua Univ, Inst Interdisciplinary Informat Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China|Tsinghua Univ, Sch Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100084, Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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