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Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos

机译：植入前胚胎中H3K4me3和H3K27me3染色质结构域的明显特征

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摘要

Histone modifications have critical roles in regulating the expression of developmental genes during embryo development in mammals(1,2). However, genome-wide analyses of histone modifications in pre-implantation embryos have been impeded by the scarcity of the required materials. Here, by using a small-scale chromatin immunoprecipitation followed by sequencing (ChIP-seq) method(3), we map the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), which are associated with gene activation and repression4,5, respectively, in mouse pre-implantation embryos. We find that the re-establishment of H3K4me3, especially on promoter regions, occurs much more rapidly than that of H3K27me3 following fertilization, which is consistent with the major wave of zygotic genome activation at the two-cell stage. Furthermore, H3K4me3 and H3K27me3 possess distinct features of sequence preference and dynamics in preimplantation embryos. Although H3K4me3 modifications occur consistently at transcription start sites, the breadth of the H3K4me3 domain is a highly dynamic feature. Notably, the broad H3K4me3 domain (wider than 5 kb) is associated with higher transcription activity and cell identity not only in pre-implantation development but also in the process of deriving embryonic stem cells from the inner cell mass and trophoblast stem cells from the trophectoderm. Compared to embryonic stem cells, we found that the bivalency (that is, co-occurrence of H3K4me3 and H3K27me3) in early embryos is relatively infrequent and unstable. Taken together, our results provide a genome-wide map of H3K4me3 and H3K27me3 modifications in pre-implantation embryos, facilitating further exploration of the mechanism for epigenetic regulation in early embryos.
机译：组蛋白修饰在哺乳动物胚胎发育过程中对调节发育基因的表达具有关键作用（1,2）。但是，由于所需材料的缺乏，阻碍了植入前胚胎中组蛋白修饰的全基因组分析。在这里，通过使用小规模的染色质免疫沉淀再测序（ChIP-seq）方法（3），我们绘制了组蛋白H3赖氨酸4三甲基化（H3K4me3）和组蛋白H3赖氨酸27三甲基化（H3K27me3）的全基因组图谱，分别与小鼠植入前胚胎中的基因激活和抑制有关4,5。我们发现，受精后，H3K4me3的重建，特别是在启动子区域的重建，比H3K27me3的重建快得多，这与两细胞阶段合子基因组激活的主要浪潮相一致。此外，H3K4me3和H3K27me3在植入前胚胎中具有独特的序列偏好和动力学特征。尽管H3K4me3修饰始终在转录起始位点发生，但是H3K4me3结构域的宽度是高度动态的。值得注意的是，宽广的H3K4me3结构域（大于5 kb）不仅在植入前发育中而且在从内细胞团衍生胚胎干细胞和从滋养外胚层滋养层干细胞衍生的过程中，都具有更高的转录活性和更高的细胞特性。 。与胚胎干细胞相比，我们发现早期胚胎的双价性（即H3K4me3和H3K27me3共存）相对较少且不稳定。综上所述，我们的结果提供了植入前胚胎中H3K4me3和H3K27me3修饰的全基因组图谱，有助于进一步探索早期胚胎的表观遗传调控机制。

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  • 来源
    《Nature》 |2016年第7621期|558-562|共5页
  • 作者

    Liu Xiaoyu; Wang Chenfei; Liu Wenqiang; Li Jingyi; Li Chong; Kou Xiaochen; Chen Jiayu; Zhao Yanhong; Gao Haibo; Wang Hong; Zhang Yong; Gao Yawei; Gao Shaorong;

  • 作者单位

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China|Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China|NIBS, Beijing 102206, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China|NIBS, Beijing 102206, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China;

    Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China|Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China|NIBS, Beijing 102206, 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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