哺乳动物胚胎发生过程中成熟配子的 3D 染色质结构和结构重编程。

3D Chromatin Structures of Mature Gametes and Structural Reprogramming during Mammalian Embryogenesis.

机构信息

CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

出版信息

Cell. 2017 Jul 13;170(2):367-381.e20. doi: 10.1016/j.cell.2017.06.029.

DOI:10.1016/j.cell.2017.06.029

PMID:28709003

Abstract

High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently. The high-order structures of both the paternal and maternal genomes in zygotes and two-cell embryos are obscure but are gradually re-established through development. The establishment of the TAD structure requires DNA replication but not zygotic genome activation. Furthermore, unmethylated CpGs are enriched in A compartment, and methylation levels are decreased to a greater extent in A compartment than in B compartment in embryos. In summary, the global reprogramming of chromatin architecture occurs during early mammalian development.

摘要

高级染色质结构在基因表达调控中发挥重要作用。然而，人们对于哺乳动物胚胎发育过程中三维染色质结构的动态变化知之甚少。我们使用优化的低细胞样本 Hi-C 方法，研究了小鼠配子和早期胚胎的三维染色质结构。结果发现，处于中期 II 阶段的成熟卵母细胞没有拓扑关联域（TAD）。在精子中，超长距离相互作用（>4 Mb）和染色体间相互作用频繁发生。合子和 2 细胞胚胎中父本和母本基因组的高级结构较为模糊，但随着发育逐渐重新建立。TAD 结构的建立需要 DNA 复制，但不需要合子基因组激活。此外，未甲基化的 CpG 富含于 A 区室中，胚胎中 A 区室的甲基化水平比 B 区室降低得更多。总之，在早期哺乳动物发育过程中，染色质结构发生了全面重编程。